ClinVar Genomic variation as it relates to human health
NM_000543.5(SMPD1):c.1071C>T (p.Ala357=)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000543.5(SMPD1):c.1071C>T (p.Ala357=)
Variation ID: 93310 Accession: VCV000093310.43
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11p15.4 11: 6392136 (GRCh38) [ NCBI UCSC ] 11: 6413366 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Oct 2, 2016 Apr 15, 2024 Feb 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000543.5:c.1071C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000534.3:p.Ala357= synonymous NM_001007593.3:c.1068C>T NP_001007594.2:p.Ala356= synonymous NM_001318087.2:c.1071C>T NP_001305016.1:p.Ala357= synonymous NM_001318088.2:c.110C>T NP_001305017.1:p.Pro37Leu missense NM_001365135.2:c.1071C>T NP_001352064.1:p.Ala357= synonymous NR_027400.3:n.1196C>T non-coding transcript variant NC_000011.10:g.6392136C>T NC_000011.9:g.6413366C>T NG_011780.1:g.6712C>T - Protein change
- P37L
- Other names
- -
- Canonical SPDI
- NC_000011.10:6392135:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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0.00339 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 0.00339
1000 Genomes Project 30x 0.00344
Exome Aggregation Consortium (ExAC) 0.00475
The Genome Aggregation Database (gnomAD), exomes 0.00513
Trans-Omics for Precision Medicine (TOPMed) 0.00566
The Genome Aggregation Database (gnomAD) 0.00571
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00654
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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SMPD1 | - | - |
GRCh38 GRCh37 |
964 | 1033 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Benign/Likely benign (3) |
criteria provided, multiple submitters, no conflicts
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Oct 5, 2020 | RCV000079188.15 | |
Benign/Likely benign (3) |
criteria provided, multiple submitters, no conflicts
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May 18, 2021 | RCV000394529.10 | |
Benign/Likely benign (3) |
criteria provided, multiple submitters, no conflicts
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Nov 1, 2023 | RCV000675396.25 | |
Likely benign (1) |
criteria provided, single submitter
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Jan 22, 2020 | RCV001249054.4 | |
Benign (1) |
criteria provided, single submitter
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Feb 1, 2024 | RCV001082924.8 | |
Likely benign (1) |
criteria provided, single submitter
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Feb 14, 2022 | RCV002415576.2 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Likely benign
(-)
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criteria provided, single submitter
Method: clinical testing
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NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV000305088.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
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Benign
(Aug 22, 2013)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000111057.8
First in ClinVar: Jan 17, 2014 Last updated: May 03, 2018 |
Number of individuals with the variant: 3
Sex: mixed
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Likely benign
(Jan 12, 2018)
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criteria provided, single submitter
Method: clinical testing
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Niemann-Pick disease, type A
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000372937.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. (less)
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Benign
(Oct 05, 2020)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001442606.1
First in ClinVar: Nov 14, 2020 Last updated: Nov 14, 2020 |
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Benign
(May 18, 2021)
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criteria provided, single submitter
Method: clinical testing
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Niemann-Pick disease, type A
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV001716378.1
First in ClinVar: Jun 15, 2021 Last updated: Jun 15, 2021 |
Sex: mixed
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Likely benign
(Feb 14, 2022)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002718915.1
First in ClinVar: Nov 29, 2022 Last updated: Nov 29, 2022 |
Comment:
This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, … (more)
This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
Number of individuals with the variant: 1
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Benign
(Feb 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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Niemann-Pick disease, type B
Niemann-Pick disease, type A
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000755907.7
First in ClinVar: May 28, 2018 Last updated: Feb 28, 2024 |
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Likely benign
(Nov 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001502022.17
First in ClinVar: Mar 14, 2021 Last updated: Apr 15, 2024 |
Comment:
SMPD1: BS2
Number of individuals with the variant: 11
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Benign
(Jan 07, 2021)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001859889.1
First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021 |
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Likely benign
(Jan 22, 2020)
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criteria provided, single submitter
Method: curation
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Sphingomyelin/cholesterol lipidosis
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
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Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
Accession: SCV001423000.2
First in ClinVar: Jul 19, 2020 Last updated: Feb 02, 2022 |
Comment:
The c.1071C>T (p.Ala357=) variant in SMPD1 (also known as p.Ala355= due to a difference in cDNA numbering) has not been previously reported in individuals with … (more)
The c.1071C>T (p.Ala357=) variant in SMPD1 (also known as p.Ala355= due to a difference in cDNA numbering) has not been previously reported in individuals with Niemann-Pick disease, but has been identified in 1.062% (110/10360) of Ashkenazi Jewish chromosomes, 0.807% (1037/128468) of European (non-Finnish) chromosomes, including 9 homozygotes, and 0.378% (134/35428) of Latino chromosomes. This variant has also been reported in ClinVar (VariationID: 93310) as a VUS by Illumina Clinical Services Laboratory, as likely benign by PreventionGenetics, and as benign by Invitae, EGL Genetic Diagnostics, and Mayo Clinic Genetic Testing Laboratories. Computational prediction tools, including splice predictors, and conservation analyses suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely benign. ACMG/AMP Criteria applied: BS1, BP4, BP7 (Richards 2015). (less)
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Benign
(Oct 22, 2015)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV000801066.1
First in ClinVar: Aug 05, 2018 Last updated: Aug 05, 2018 |
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Benign
(Mar 29, 2017)
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no assertion criteria provided
Method: clinical testing
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Niemann-Pick Disease, Types A/B
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002092260.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=SMPD1 | - | - | - | - |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/1be307c2-407c-4c39-9891-b1805248daaa | - | - | - | - |
Text-mined citations for rs72896268 ...
HelpRecord last updated Apr 15, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.