NM_002047.4(GARS1):c.979G>A (p.Gly327Arg) AND Neuronopathy, distal hereditary motor, type 5A

Germline classification:: Pathogenic (1 submission)
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:: RCV001823170.3

Allele description [Variation Report for NM_002047.4(GARS1):c.979G>A (p.Gly327Arg)]

NM_002047.4(GARS1):c.979G>A (p.Gly327Arg)

Gene:

GARS1:glycyl-tRNA synthetase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p14.3

Genomic location:

Preferred name:

NM_002047.4(GARS1):c.979G>A (p.Gly327Arg)

HGVS:

NC_000007.14:g.30612193G>A
NG_007942.1:g.22629G>A
NM_001316772.1:c.817G>A
NM_002047.4:c.979G>AMANE SELECT
NP_001303701.1:p.Gly273Arg
NP_002038.2:p.Gly327Arg
LRG_243t1:c.979G>A
LRG_243:g.22629G>A
NC_000007.13:g.30651809G>A
NM_002047.2:c.979G>A
NM_002047.3:c.[979G>A]

Protein change:

G273R

Links:

dbSNP: rs1584034430

NCBI 1000 Genomes Browser:

rs1584034430

Molecular consequence:

NM_001316772.1:c.817G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_002047.4:c.979G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Neuronopathy, distal hereditary motor, type 5A (HMND5)
Synonyms:: DHMN VA; NEURONOPATHY, DISTAL HEREDITARY MOTOR, AUTOSOMAL DOMINANT 5; Distal Spinal Muscular Atrophy V
Identifiers:: MONDO: MONDO:0015353; MedGen: C5399969; Orphanet: 139536; OMIM: 600794

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002073344	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	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

SCV002073344

Neuberg Centre For Genomic Medicine, NCGM

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

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	yes	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

Details of each submission

From Neuberg Centre For Genomic Medicine, NCGM, SCV002073344.1

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

Description

The missense variant p.G327R in GARS1 (NM_002047.4) has been been reported previously in two unrelated patients hereditary motor neuropathy. Functional studies suggest a damaging effect (Lee DC et al, 2020). The variant has been submitted to ClinVar as Uncertain significance. The p.G327R variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. The p.G327R missense variant is predicted to be damaging by both SIFT and PolyPhen2. The glycine residue at codon 327 of GARS1 is conserved in all mammalian species. The nucleotide c.979 in GARS1 is predicted conserved by GERP++ and PhyloP across 100 vertebrates. 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	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 6, 2024

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