VCV000541793.12 - ClinVar

NM_006642.5(SDCCAG8):c.518T>C (p.Leu173Pro)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Uncertain significance
Uncertain significance (5)

5 out of 6 submissions contributed to this classification

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.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_006642.5(SDCCAG8):c.518T>C (p.Leu173Pro)

Variation ID: 541793 Accession: VCV000541793.12

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 1q43 1: 243286369 (GRCh38) [ NCBI UCSC ] 1: 243449671 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	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	May 28, 2018	Jan 13, 2025	Oct 22, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_006642.5:c.518T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_006633.1:p.Leu173Pro	missense
NM_001350246.2:c.-595T>C		5 prime UTR
NM_001350247.2:c.-483T>C		5 prime UTR
NM_001350248.2:c.518T>C	NP_001337177.1:p.Leu173Pro	missense
NM_001350249.2:c.224T>C	NP_001337178.1:p.Leu75Pro	missense
NM_001350251.2:c.-856T>C		5 prime UTR
NC_000001.11:g.243286369T>C
NC_000001.10:g.243449671T>C
NG_027811.1:g.35365T>C

... more HGVS ... less HGVS

Protein change

L173P, L75P

Other names

Canonical SPDI

NC_000001.11:243286368:T:C

Global minor allele frequency (GMAF) Help The 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.

0.00020 (C)

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD) 0.00003

Trans-Omics for Precision Medicine (TOPMed) 0.00003

The Genome Aggregation Database (gnomAD), exomes 0.00007

Exome Aggregation Consortium (ExAC) 0.00009

1000 Genomes Project 30x 0.00016

1000 Genomes Project 0.00020

Links

ClinGen: CA1483327 dbSNP: rs541533278 VarSome

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
Gene	OMIM	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.
SDCCAG8		Gene associated with autosomal recessive phenotype	No evidence available	GRCh38 GRCh38 GRCh37	754	959

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.
Bardet-Biedl syndrome 16 Senior-Loken syndrome 7	Uncertain significance (2)	criteria provided, multiple submitters, no conflicts	Feb 17, 2022	RCV000652118.8
Bardet-Biedl syndrome 16	Uncertain significance (1)	criteria provided, single submitter	Jan 12, 2018	RCV001099444.4
Senior-Loken syndrome 7	Uncertain significance (1)	criteria provided, single submitter	Jan 12, 2018	RCV001099445.4
SDCCAG8-related disorder	Uncertain significance (1)	no assertion criteria provided	Sep 13, 2024	RCV004735720.1
Inborn genetic diseases	Uncertain significance (1)	criteria provided, single submitter	Oct 22, 2024	RCV004957960.1

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.	Expand all rows Collapse all rows 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.
Uncertain significance (Jan 12, 2018) C Contributing to aggregate classification	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Bardet-Biedl syndrome 16	Illumina Laboratory Services, Illumina Accession: SCV001255899.1 First in ClinVar: May 31, 2020 Last updated: May 31, 2020	Comment: show 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Uncertain significance (Jan 12, 2018) C Contributing to aggregate classification	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Senior-Loken syndrome 7	Illumina Laboratory Services, Illumina Accession: SCV001255900.1 First in ClinVar: May 31, 2020 Last updated: May 31, 2020	Comment: show 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Uncertain significance (Feb 17, 2022) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Senior-Loken syndrome 7 Bardet-Biedl syndrome 16	Fulgent Genetics, Fulgent Genetics Accession: SCV000894773.2 First in ClinVar: Mar 31, 2019 Last updated: Dec 31, 2022	Publications: PubMed (1) PubMed: 25741868 DOI: 10.1038/gim.2015.30 DOI: 10.1038/gim.2015.30 pmc: 4544753 pmc: 4544753 Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown

Uncertain significance (Oct 27, 2021) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Bardet-Biedl syndrome 16 Senior-Loken syndrome 7	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000773986.4 First in ClinVar: May 28, 2018 Last updated: Feb 07, 2023	Comment: show This sequence change replaces leucine, a(n) neutral and non-polar amino acid, with proline, a(n) neutral and non-polar amino acid, at codon 173 of the SDCCAG8 protein (p.Leu173Pro). This variant is present in population databases (rs541533278, gnomAD 0.01%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with SDCCAG8-related conditions. ClinVar contains an entry for this variant (Variation ID: 541793). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Uncertain significance (Oct 22, 2024) C Contributing to aggregate classification	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Inborn genetic diseases	Ambry Genetics Accession: SCV005494413.1 First in ClinVar: Jan 13, 2025 Last updated: Jan 13, 2025	Comment: show The c.518T>C (p.L173P) alteration is located in exon 5 (coding exon 5) of the SDCCAG8 gene. This alteration results from a T to C substitution at nucleotide position 518, causing the leucine (L) at amino acid position 173 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Uncertain significance (Sep 13, 2024) N Not contributing to aggregate classification	no assertion criteria provided	SDCCAG8-related condition	PreventionGenetics, part of Exact Sciences Accession: SCV005360264.1 First in ClinVar: Oct 08, 2024 Last updated: Oct 08, 2024	Comment: show The SDCCAG8 c.518T>C variant is predicted to result in the amino acid substitution p.Leu173Pro. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.012% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

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 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

Comment:

This sequence change replaces leucine, a(n) neutral and non-polar amino acid, with proline, a(n) neutral and non-polar amino acid, at codon 173 of the SDCCAG8 protein (p.Leu173Pro). This variant is present in population databases (rs541533278, gnomAD 0.01%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with SDCCAG8-related conditions. ClinVar contains an entry for this variant (Variation ID: 541793). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

Comment:

The c.518T>C (p.L173P) alteration is located in exon 5 (coding exon 5) of the SDCCAG8 gene. This alteration results from a T to C substitution at nucleotide position 518, causing the leucine (L) at amino acid position 173 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

Comment:

The SDCCAG8 c.518T>C variant is predicted to result in the amino acid substitution p.Leu173Pro. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.012% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs541533278 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Apr 13, 2026