NM_014236.4(GNPAT):c.631C>T (p.Arg211Cys) AND Rhizomelic chondrodysplasia punctata

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 22, 2023
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:: RCV003234895.1

Allele description [Variation Report for NM_014236.4(GNPAT):c.631C>T (p.Arg211Cys)]

NM_014236.4(GNPAT):c.631C>T (p.Arg211Cys)

Gene:

GNPAT:glyceronephosphate O-acyltransferase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q42.2

Genomic location:

Preferred name:

NM_014236.4(GNPAT):c.631C>T (p.Arg211Cys)

HGVS:

NC_000001.11:g.231265355C>T
NG_008240.2:g.29183C>T
NM_001316350.2:c.448C>T
NM_014236.3:c.631C>T
NM_014236.4:c.631C>TMANE SELECT
NP_001303279.1:p.Arg150Cys
NP_055051.1:p.Arg211Cys
NC_000001.10:g.231401101C>T
NG_008240.1:g.29183C>T
NM_014236.4:c.631C>T
O15228:p.Arg211Cys

Protein change:

R150C; ARG211CYS

Links:

UniProtKB: O15228#VAR_006357; OMIM: 602744.0002; dbSNP: rs121434440

NCBI 1000 Genomes Browser:

rs121434440

Molecular consequence:

NM_001316350.2:c.448C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_014236.4:c.631C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Rhizomelic chondrodysplasia punctata (RCDP)
Identifiers:: MONDO: MONDO:0015776; MedGen: C0282529; OMIM: PS215100

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003933904	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (May 22, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003933904

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(May 22, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

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

Etherphospholipid biosynthesis and dihydroxyactetone-phosphate acyltransferase: resolution of the genomic organization of the human gnpat gene and its use in the identification of novel mutations.

Ofman R, Lajmir S, Wanders RJ.

Biochem Biophys Res Commun. 2001 Mar 2;281(3):754-60.

PubMed [citation]

PMID:: 11237722

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV003933904.1

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

Description

Variant summary: GNPAT c.631C>T (p.Arg211Cys) results in a non-conservative amino acid change located in the Phospholipid/glycerol acyltransferase (IPR002123) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251464 control chromosomes. c.631C>T has been reported in the literature in individuals affected with Rhizomelic Chondrodysplasia Punctata (Ofman_2001). At least one publication reports experimental evidence evaluating an impact on protein function indicating no GNPAT enzyme activity in a homozygous individual (Ofman_2001). Another variant affecting the same amino acid (p.Arg211His, pathogenic in ClinVar) has been observed in homozygous individuals with no GNPAT activity suggesting an important role of this variant in disease. The following publication have been ascertained in the context of this evaluation (PMID: 11237722).No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely 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: Dec 30, 2023

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