rs1553613078

Variant names:

• chr3-38698342-CATACC-TGGAGTAGAT
• rs1553613078
• NM_006514.4:c.4873_4878delGGTATGinsATCTACTCCA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006514.4(SCN10A):​c.4873_4878delGGTATGinsATCTACTCCA​(p.Gly1625IlefsTer56) variant causes a frameshift, missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SCN10A NM_006514.4 frameshift, missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.31

Genes affected

SCN10A (HGNC:10582): (sodium voltage-gated channel alpha subunit 10) The protein encoded by this gene is a tetrodotoxin-resistant voltage-gated sodium channel alpha subunit. The properties of the channel formed by the encoded transmembrane protein can be altered by interaction with different beta subunits. This protein may be involved in the onset of pain associated with peripheral neuropathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN10A	NM_006514.4	c.4873_4878delGGTATGinsATCTACTCCA	p.Gly1625IlefsTer56	frameshift_variant, missense_variant	Exon 28 of 28	ENST00000449082.3	NP_006505.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN10A	ENST00000449082.3	c.4873_4878delGGTATGinsATCTACTCCA	p.Gly1625IlefsTer56	frameshift_variant, missense_variant	Exon 28 of 28	1	NM_006514.4	ENSP00000390600.2
SCN10A	ENST00000643924.1	c.4870_4875delGGTATGinsATCTACTCCA	p.Gly1624IlefsTer56	frameshift_variant, missense_variant	Exon 27 of 27			ENSP00000495595.1
SCN10A	ENST00000655275.1	c.4897_4902delGGTATGinsATCTACTCCA	p.Gly1633IlefsTer56	frameshift_variant, missense_variant	Exon 28 of 28			ENSP00000499510.1

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Brugada syndrome Uncertain:1

Sep 01, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with SCN10A-related conditions. This variant is present in population databases (rs759319080, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Gly1625Ilefs*56) in the SCN10A gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 332 amino acid(s) of the SCN10A protein. -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1553613078; hg19: chr3-38739833;