rs769940455

chr12-51745885-CTTT-Cchr12-51745885-CTTT-CTchr12-51745885-CTTT-CTTchr12-51745885-CTTT-CTTTTchr12-51745885-CTTT-CTTTTTchr12-51745885-CTTT-CTTTTTT

Variant summary

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

The NM_014191.4(SCN8A):c.1999-7_1999-5del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000148 in 1,084,032 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: SCN8A NM_014191.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.316

Genes affected

SCN8A (HGNC:10596): (sodium voltage-gated channel alpha subunit 8) This gene encodes a member of the sodium channel alpha subunit gene family. The encoded protein forms the ion pore region of the voltage-gated sodium channel. This protein is essential for the rapid membrane depolarization that occurs during the formation of the action potential in excitable neurons. Mutations in this gene are associated with cognitive disability, pancerebellar atrophy and ataxia. Alternate splicing results in multiple transcript variants.[provided by RefSeq, May 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCN8A	NM_001330260.2	c.1999-7_1999-5del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000627620.5
SCN8A	NM_014191.4	c.1999-7_1999-5del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000354534.11
SCN8A	NM_001177984.3	c.1999-7_1999-5del		splice_polypyrimidine_tract_variant, intron_variant
SCN8A	NM_001369788.1	c.1999-7_1999-5del		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCN8A	ENST00000354534.11	c.1999-7_1999-5del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_014191.4	P4
SCN8A	ENST00000627620.5	c.1999-7_1999-5del		splice_polypyrimidine_tract_variant, intron_variant		5	NM_001330260.2	A1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.0000499 AC: 4 AN: 80108 Hom.: 0 AF XY: 0.0000702 AC XY: 3 AN XY: 42762

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000111

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000783

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000148 AC: 16 AN: 1084032 Hom.: 0 AF XY: 0.0000186 AC XY: 10 AN XY: 538464

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000405

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000666

Gnomad4 FIN exome AF: 0.0000258

Gnomad4 NFE exome AF: 0.0000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs769940455; hg19: chr12-52139669;