NM_001543.5(NDST1):c.1831G>A (p.Gly611Ser) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:: Dec 1, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002279948.11

Allele description

NM_001543.5(NDST1):c.1831G>A (p.Gly611Ser)

Gene:

NDST1:N-deacetylase and N-sulfotransferase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q33.1

Genomic location:

Preferred name:

NM_001543.5(NDST1):c.1831G>A (p.Gly611Ser)

HGVS:

NC_000005.10:g.150541651G>A
NG_041806.1:g.48874G>A
NM_001301063.2:c.1831G>A
NM_001543.5:c.1831G>AMANE SELECT
NP_001287992.1:p.Gly611Ser
NP_001534.1:p.Gly611Ser
NC_000005.9:g.149921213G>A
NM_001543.4:c.1831G>A
P52848:p.Gly611Ser

Protein change:

G611S; GLY611SER

Links:

UniProtKB: P52848#VAR_072646; OMIM: 600853.0004; dbSNP: rs606231459

NCBI 1000 Genomes Browser:

rs606231459

Molecular consequence:

NM_001301063.2:c.1831G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001543.5:c.1831G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002568838	Laboratoire de Génétique Moléculaire, CHU Bordeaux	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003439241	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Mar 23, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 25125150, 27620904, 28492532
SCV003935846	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Jun 21, 2023)	germline	clinical testing	Citation Link,
SCV004701944	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Likely pathogenic (Dec 1, 2023)	germline	clinical testing	Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	3	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

NDST1 missense mutations in autosomal recessive intellectual disability.

Reuter MS, Musante L, Hu H, Diederich S, Sticht H, Ekici AB, Uebe S, Wienker TF, Bartsch O, Zechner U, Oppitz C, Keleman K, Jamra RA, Najmabadi H, Schweiger S, Reis A, Kahrizi K.

Am J Med Genet A. 2014 Nov;164A(11):2753-63. doi: 10.1002/ajmg.a.36723. Epub 2014 Aug 14.

PubMed [citation]

PMID:: 25125150

See all PubMed Citations (4)

Details of each submission

From Laboratoire de Génétique Moléculaire, CHU Bordeaux, SCV002568838.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Invitae, SCV003439241.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt NDST1 protein function. ClinVar contains an entry for this variant (Variation ID: 161412). This missense change has been observed in individuals with clinical features of intellectual disability (PMID: 25125150, 27620904; Invitae). This variant is present in population databases (rs606231459, gnomAD 0.002%). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 611 of the NDST1 protein (p.Gly611Ser).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From GeneDx, SCV003935846.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25125150, 31589614, 27870114, 27620904, 35887114)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From CeGaT Center for Human Genetics Tuebingen, SCV004701944.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	not provided	not provided	clinical testing	not provided

Description

NDST1: PM1, PM2, PM3, PP3

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		3	not provided	not provided	not provided

Last Updated: Jul 15, 2024

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