NM_000171.4(GLRA1):c.1040G>C (p.Arg347Thr) AND Hereditary hyperekplexia

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 4, 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:: RCV001047521.6

Allele description [Variation Report for NM_000171.4(GLRA1):c.1040G>C (p.Arg347Thr)]

NM_000171.4(GLRA1):c.1040G>C (p.Arg347Thr)

Gene:

GLRA1:glycine receptor alpha 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q33.1

Genomic location:

Preferred name:

NM_000171.4(GLRA1):c.1040G>C (p.Arg347Thr)

HGVS:

NC_000005.10:g.151828940C>G
NG_011764.1:g.100897G>C
NM_000171.4:c.1040G>CMANE SELECT
NM_001146040.2:c.1040G>C
NM_001292000.2:c.791G>C
NP_000162.2:p.Arg347Thr
NP_001139512.1:p.Arg347Thr
NP_001278929.1:p.Arg264Thr
NC_000005.9:g.151208501C>G
NM_000171.3:c.1040G>C

Protein change:

R264T

Links:

dbSNP: rs147156518

NCBI 1000 Genomes Browser:

rs147156518

Molecular consequence:

NM_000171.4:c.1040G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001146040.2:c.1040G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001292000.2:c.791G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary hyperekplexia
Synonyms:: Hyperexplexia, hereditary
Identifiers:: MONDO: MONDO:0021022; MedGen: C1835614; OMIM: PS149400

Recent activity

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TEX40 (63)
Protein
cytochrome c oxidase subunit I, partial (mitochondrion) [Prodotia iostoma]
cytochrome c oxidase subunit I, partial (mitochondrion) [Prodotia iostoma]
gi|2067073281|gb|QXN56186.1|

Protein
Macrophages infected with Salmonella (SHS)(I)
Macrophages infected with Salmonella (SHS)(I)
Accession: GDS80

GEO DataSets
Related DataSets for GEO Profiles (Select 489064) (1)
GEO DataSets
PREDICTED: Homo sapiens F-box and WD repeat domain containing 5 (FBXW5), transcr...
PREDICTED: Homo sapiens F-box and WD repeat domain containing 5 (FBXW5), transcript variant X5, mRNA
gi|2462625028|ref|XM_054363122.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001211485	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 4, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001211485

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 4, 2023)

germline

clinical testing

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

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001211485.5

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

Description

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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on GLRA1 protein function. ClinVar contains an entry for this variant (Variation ID: 844620). This variant has not been reported in the literature in individuals affected with GLRA1-related conditions. This variant is present in population databases (rs147156518, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with threonine, which is neutral and polar, at codon 347 of the GLRA1 protein (p.Arg347Thr).

#	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: Sep 29, 2024

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Relating variation to medicine