NM_024312.5(GNPTAB):c.1196C>T (p.Ser399Phe) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 22, 2024
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000820177.14

Allele description [Variation Report for NM_024312.5(GNPTAB):c.1196C>T (p.Ser399Phe)]

NM_024312.5(GNPTAB):c.1196C>T (p.Ser399Phe)

Gene:

GNPTAB:N-acetylglucosamine-1-phosphate transferase subunits alpha and beta [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q23.2

Genomic location:

Preferred name:

NM_024312.5(GNPTAB):c.1196C>T (p.Ser399Phe)

HGVS:

NC_000012.12:g.101770109G>A
NG_021243.1:g.65759C>T
NM_024312.5:c.1196C>TMANE SELECT
NP_077288.2:p.Ser399Phe
NC_000012.11:g.102163887G>A
NM_024312.4:c.1196C>T
Q3T906:p.Ser399Phe

Nucleotide change:

AY687932:c.1196C>T

Protein change:

S399F

Links:

UniProtKB: Q3T906#VAR_062808; dbSNP: rs281865026

NCBI 1000 Genomes Browser:

rs281865026

Molecular consequence:

NM_024312.5:c.1196C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Mucolipidosis type II
Synonyms:: ML II ALPHA/BETA; I cell disease; Mucolipidosis 2; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009650; MedGen: C2673377; Orphanet: 576; OMIM: 252500

Name:: Pseudo-Hurler polydystrophy (ML3)
Synonyms:: ML III; ML III ALPHA/BETA; Mucolipidosis type 3A; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0018931; MedGen: C0033788; Orphanet: 577; OMIM: 252600

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000960877	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 22, 2024)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 16630736, 19659762, 23566849, 27710913, 24375680, 24550498, 25505245, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000960877

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 22, 2024)

germline

clinical testing

PubMed (8)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

When Mucolipidosis III meets Mucolipidosis II: GNPTA gene mutations in 24 patients.

Bargal R, Zeigler M, Abu-Libdeh B, Zuri V, Mandel H, Ben Neriah Z, Stewart F, Elcioglu N, Hindi T, Le Merrer M, Bach G, Raas-Rothschild A.

Mol Genet Metab. 2006 Aug;88(4):359-63. Epub 2006 Apr 21. Erratum in: Mol Genet Metab. 2007 Jul;91(3):299.

PubMed [citation]

PMID:: 16630736

Molecular analysis of the GNPTAB and GNPTG genes in 13 patients with mucolipidosis type II or type III - identification of eight novel mutations.

Encarnação M, Lacerda L, Costa R, Prata MJ, Coutinho MF, Ribeiro H, Lopes L, Pineda M, Ignatius J, Galvez H, Mustonen A, Vieira P, Lima MR, Alves S.

Clin Genet. 2009 Jul;76(1):76-84. doi: 10.1111/j.1399-0004.2009.01185.x.

PubMed [citation]

PMID:: 19659762

See all PubMed Citations (8)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000960877.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 399 of the GNPTAB protein (p.Ser399Phe). This variant is present in population databases (rs281865026, gnomAD 0.003%). This missense change has been observed in individual(s) with GNPTAB-related conditions (PMID: 16630736, 19659762, 23566849, 27710913). ClinVar contains an entry for this variant (Variation ID: 38413). 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 GNPTAB protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects GNPTAB function (PMID: 24375680, 24550498, 25505245). For these reasons, this variant has been classified as Pathogenic.

#	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

Last Updated: Nov 3, 2024

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