NM_003098.3(SNTA1):c.430T>G (p.Ser144Ala) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Apr 7, 2017
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:: RCV000489834.2

Allele description [Variation Report for NM_003098.3(SNTA1):c.430T>G (p.Ser144Ala)]

NM_003098.3(SNTA1):c.430T>G (p.Ser144Ala)

Gene:

SNTA1:syntrophin alpha 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

20q11.21

Genomic location:

Preferred name:

NM_003098.3(SNTA1):c.430T>G (p.Ser144Ala)

HGVS:

NC_000020.11:g.33438907A>C
NG_011622.1:g.9986T>G
NM_003098.3:c.430T>GMANE SELECT
NP_003089.1:p.Ser144Ala
NP_003089.1:p.Ser144Ala
LRG_332t1:c.430T>G
LRG_332:g.9986T>G
LRG_332p1:p.Ser144Ala
NC_000020.10:g.32026713A>C
NM_003098.2:c.430T>G

Protein change:

S144A

Links:

dbSNP: rs142978180

NCBI 1000 Genomes Browser:

rs142978180

Molecular consequence:

NM_003098.3:c.430T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000577193	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Uncertain significance (Apr 7, 2017)	germline	clinical testing	Citation Link,
SCV001554333	Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR) See additional submitters Franklin by Genoox	no assertion criteria provided	Uncertain significance	unknown	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000577193

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Uncertain significance
(Apr 7, 2017)

germline

clinical testing

Citation Link,

SCV001554333

Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria provided

Uncertain significance

unknown

clinical testing

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
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV000577193.4

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

Description

A variant of uncertain significance has been identified in the SNTA1 gene. The S144A variant has been previously reported in one case of sudden infant death syndrome (SIDS) (Brion et al., 2014); however, this infant also harbored an additional missense variant in the KCNE1 gene and no further clinical details or segregation studies were described. The S144A variant has also been observed in 8/10406 (0.08%) alleles from individuals of African ancestry in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The S144A variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Additionally, this substitution occurs at a position that is conserved in mammals. Nevertheless, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.

#	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

From Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV001554333.1

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

Description

The SNTA1 p.S144A variant was not identified in the literature but was identified in dbSNP (ID: rs142978180) and ClinVar (classified as uncertain significance by GeneDx and Ambry Genetics). The variant was identified in control databases in 15 of 282886 chromosomes at a frequency of 0.00005302, and was observed only in the African population in 15 of 24970 chromosomes (freq: 0.0006007) (Genome Aggregation Database March 6, 2019, v2.1.1). The p.S144 residue is conserved in mammals and computational analyses (MUT Assesor, PolyPhen-2, SIFT, MutationTaster, Revel, FATHMM, MetaLR, DANN) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (Splice AI exome) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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