NM_000344.4(SMN1):c.865T>A (p.Cys289Ser) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 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:: RCV000588115.3

Allele description [Variation Report for NM_000344.4(SMN1):c.865T>A (p.Cys289Ser)]

NM_000344.4(SMN1):c.865T>A (p.Cys289Ser)

Gene:

SMN1:survival of motor neuron 1, telomeric [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q13.2

Genomic location:

Preferred name:

NM_000344.4(SMN1):c.865T>A (p.Cys289Ser)

HGVS:

NC_000005.10:g.70951971T>A
NG_008691.1:g.32031T>A
NM_000344.4:c.865T>AMANE SELECT
NM_001297715.1:c.835-468T>A
NM_022874.2:c.769T>A
NP_000335.1:p.Cys289Ser
NP_000335.1:p.Cys289Ser
NP_075012.1:p.Cys257Ser
LRG_676t1:c.865T>A
LRG_676:g.32031T>A
LRG_676p1:p.Cys289Ser
NC_000005.9:g.70247798T>A
NM_000344.3:c.865T>A

Protein change:

C257S

Links:

dbSNP: rs187925143

NCBI 1000 Genomes Browser:

rs187925143

Molecular consequence:

NM_001297715.1:c.835-468T>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000344.4:c.865T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_022874.2:c.769T>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000696583	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Dec 9, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000696583

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Dec 9, 2022)

germline

clinical testing

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

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

Pan-ethnic carrier screening and prenatal diagnosis for spinal muscular atrophy: clinical laboratory analysis of >72,400 specimens.

Sugarman EA, Nagan N, Zhu H, Akmaev VR, Zhou Z, Rohlfs EM, Flynn K, Hendrickson BC, Scholl T, Sirko-Osadsa DA, Allitto BA.

Eur J Hum Genet. 2012 Jan;20(1):27-32. doi: 10.1038/ejhg.2011.134. Epub 2011 Aug 3.

PubMed [citation]

PMID:: 21811307
PMCID:: PMC3234503

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000696583.3

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

Description

Variant summary: SMN1 c.865T>A (p.Cys289Ser) results in a non-conservative amino acid change located in the Survival motor neuron C-Terminal tail domain of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0002 in 385156 control chromosomes, predominantly at a frequency of 0.00098 within the Latino subpopulation in the gnomAD database, including 1 homozygote. This frequency is not higher than expected for a pathogenic variant in SMN1 causing Spinal Muscular Atrophy (0.0002 vs 0.0025), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.865T>A in individuals affected with Spinal Muscular Atrophy and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as 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: Dec 24, 2023

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