NM_005866.4(SIGMAR1):c.92G>A (p.Gly31Asp) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 21, 2022
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:: RCV000641751.10

Allele description [Variation Report for NM_005866.4(SIGMAR1):c.92G>A (p.Gly31Asp)]

NM_005866.4(SIGMAR1):c.92G>A (p.Gly31Asp)

Genes:

LOC130001681:ATAC-STARR-seq lymphoblastoid silent region 19853 [Gene]
SIGMAR1:sigma non-opioid intracellular receptor 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9p13.3

Genomic location:

Preferred name:

NM_005866.4(SIGMAR1):c.92G>A (p.Gly31Asp)

HGVS:

NC_000009.12:g.34637606C>T
NG_029945.2:g.5166G>A
NG_181127.1:g.170C>T
NM_001282205.2:c.92G>A
NM_001282206.2:c.-162G>A
NM_001282207.2:c.91+1G>A
NM_001282208.2:c.92G>A
NM_001282209.2:c.92G>A
NM_005866.4:c.92G>AMANE SELECT
NM_147157.3:c.92G>A
NP_001269134.1:p.Gly31Asp
NP_001269137.1:p.Gly31Asp
NP_001269138.1:p.Gly31Asp
NP_005857.1:p.Gly31Asp
NP_671513.1:p.Gly31Asp
NC_000009.11:g.34637603C>T
NM_005866.2:c.92G>A
NM_005866.3:c.92G>A
NR_104108.2:n.182G>A

Protein change:

G31D

Links:

dbSNP: rs532632647

NCBI 1000 Genomes Browser:

rs532632647

Molecular consequence:

NM_001282206.2:c.-162G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001282205.2:c.92G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282208.2:c.92G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282209.2:c.92G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_005866.4:c.92G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_147157.3:c.92G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_104108.2:n.182G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001282207.2:c.91+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Autosomal recessive distal spinal muscular atrophy 2
Synonyms:: NEURONOPATHY, DISTAL HEREDITARY MOTOR, JERASH TYPE; NEUROPATHY, DISTAL HEREDITARY MOTOR, JERASH TYPE; Hereditary motor neuropathy, Jerash type; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011585; MedGen: C1854023; Orphanet: 139552; OMIM: 605726

Name:: Amyotrophic lateral sclerosis type 16
Synonyms:: Amyotrophic lateral sclerosis 16, juvenile
Identifiers:: MONDO: MONDO:0013715; MedGen: C3280587; Orphanet: 300605; OMIM: 614373

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000763399	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 21, 2022)	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

SCV000763399

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 21, 2022)

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, SCV000763399.7

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

Description

This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 31 of the SIGMAR1 protein (p.Gly31Asp). This variant is present in population databases (rs532632647, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with SIGMAR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 534261). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15". The aspartic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.

#	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: Oct 20, 2024

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