NM_003334.4(UBA1):c.31C>T (p.Arg11Cys) AND Infantile-onset X-linked spinal muscular atrophy

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 9, 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:: RCV001957186.5

Allele description

NM_003334.4(UBA1):c.31C>T (p.Arg11Cys)

Genes:

LOC126863253:CDK7 strongly-dependent group 2 enhancer GRCh37_chrX:47057593-47058792 [Gene]
UBA1:ubiquitin like modifier activating enzyme 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xp11.3

Genomic location:

Preferred name:

NM_003334.4(UBA1):c.31C>T (p.Arg11Cys)

HGVS:

NC_000023.11:g.47198833C>T
NG_009161.1:g.13034C>T
NM_003334.4:c.31C>TMANE SELECT
NM_153280.3:c.31C>T
NP_003325.2:p.Arg11Cys
NP_695012.1:p.Arg11Cys
NC_000023.10:g.47058232C>T

Protein change:

R11C

Links:

dbSNP: rs1556786387

NCBI 1000 Genomes Browser:

rs1556786387

Molecular consequence:

NM_003334.4:c.31C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_153280.3:c.31C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Infantile-onset X-linked spinal muscular atrophy
Synonyms:: ARTHROGRYPOSIS, X-LINKED, TYPE I; SPINAL MUSCULAR ATROPHY, X-LINKED LETHAL INFANTILE; Arthrogryposis multiplex congenita, distal, X-linked; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010532; MedGen: C1844934; Orphanet: 1145; OMIM: 301830

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002206777	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 9, 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

SCV002206777

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 9, 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 Invitae, SCV002206777.3

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

Description

This variant is present in population databases (no rsID available, gnomAD 0.008%), including at least one homozygous and/or hemizygous individual. This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 11 of the UBA1 protein (p.Arg11Cys). This variant has not been reported in the literature in individuals affected with UBA1-related conditions. 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 1424507).

#	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: Feb 28, 2024

ClinVar

Relating variation to medicine