rs1553472800

chr2-166198890-TGTA-AGTT

Variant summary

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

The NM_001365536.1(SCN9A):c.5746_5749delinsAACT(p.Tyr1916_Ile1917delinsAsnLeu) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. Y1916Y) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCN9A NM_001365536.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.27

Genes affected

SCN9A (HGNC:10597): (sodium voltage-gated channel alpha subunit 9) This gene encodes a voltage-gated sodium channel which plays a significant role in nociception signaling. Mutations in this gene have been associated with primary erythermalgia, channelopathy-associated insensitivity to pain, and paroxysmal extreme pain disorder. [provided by RefSeq, Aug 2009]

SCN1A-AS1 (HGNC:54069): (SCN1A and SCN9A antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCN9A	NM_001365536.1	c.5746_5749delinsAACT	p.Tyr1916_Ile1917delinsAsnLeu	missense_variant	27/27	ENST00000642356.2
SCN1A-AS1	NR_110260.1	n.432-749_432-746delinsAGTT		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCN9A	ENST00000642356.2	c.5746_5749delinsAACT	p.Tyr1916_Ile1917delinsAsnLeu	missense_variant	27/27		NM_001365536.1	P1
SCN1A-AS1	ENST00000651574.1	n.1110-749_1110-746delinsAGTT		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Generalized epilepsy with febrile seizures plus, type 7;C2752089:Neuropathy, hereditary sensory and autonomic, type 2A Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

May 08, 2019

In summary, this variant is a rare in-frame deletion and insertion with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted and inserted amino acids is currently unknown. This variant is reported as two separate single-nucleotide changes in population databases (c.5713T>A, ExAC 0.002% and c.5716A>T, ExAC 0.002%). In all reads displayed in the ExAC browser, these two variants are in cis. This recapitulates the variant observed here (c.5713_5716delinsAACT). However, this frequency data may be unreliable, as metrics indicate poor quality at position c.5716 in the ExAC database. This variant has not been reported in the literature in individuals with a SCN9A-related disease. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a SCN9A-related disease. This sequence change deletes and inserts 4 nucleotides in exon 27 of the SCN9A mRNA (c.5713_5716delinsAACT). This leads to a deletion and insertion of 2 amino acid residues in the SCN9A protein (p.Tyr1905_Ile1906delinsAsnLeu) but otherwise preserves the integrity of the reading frame. -

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: rs1553472800; hg19: chr2-167055400;