NM_003334.4(UBA1):c.2351G>A (p.Arg784Gln) AND Infantile-onset X-linked spinal muscular atrophy

Germline classification:: Benign (2 submissions)
Last evaluated:: Jan 20, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000640822.12

Allele description [Variation Report for NM_003334.4(UBA1):c.2351G>A (p.Arg784Gln)]

NM_003334.4(UBA1):c.2351G>A (p.Arg784Gln)

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.2351G>A (p.Arg784Gln)

HGVS:

NC_000023.11:g.47211112G>A
NG_009161.1:g.25313G>A
NM_003334.4:c.2351G>AMANE SELECT
NM_153280.3:c.2351G>A
NP_003325.2:p.Arg784Gln
NP_695012.1:p.Arg784Gln
NC_000023.10:g.47070511G>A
NM_003334.3:c.2351G>A

Protein change:

R784Q

Links:

dbSNP: rs148382699

NCBI 1000 Genomes Browser:

rs148382699

Molecular consequence:

NM_003334.4:c.2351G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_153280.3:c.2351G>A - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000762423	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Benign (Jan 20, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001330982	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Benign (Jan 13, 2018)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000762423

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Benign
(Jan 20, 2024)

germline

clinical testing

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

SCV001330982

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Benign
(Jan 13, 2018)

germline

clinical testing

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

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000762423.6

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

#	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

From Illumina Laboratory Services, Illumina, SCV001330982.1

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

Description

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

#	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: Mar 5, 2024

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