rs17126078

Positions:

• chr12-51779543-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330260.2(SCN8A):​c.3820-1106T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,124 control chromosomes in the GnomAD database, including 1,451 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.12 (1451 hom., cov: 32)
• Consequence: SCN8A NM_001330260.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0950

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN8A	NM_001330260.2	c.3820-1106T>C		intron_variant		ENST00000627620.5	NP_001317189.1
SCN8A	NM_014191.4	c.3820-1106T>C		intron_variant		ENST00000354534.11	NP_055006.1
SCN8A	NM_001177984.3	c.3819+5181T>C		intron_variant			NP_001171455.1
SCN8A	NM_001369788.1	c.3819+5181T>C		intron_variant			NP_001356717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN8A	ENST00000354534.11	c.3820-1106T>C		intron_variant		1	NM_014191.4	ENSP00000346534.4
SCN8A	ENST00000627620.5	c.3820-1106T>C		intron_variant		5	NM_001330260.2	ENSP00000487583.2
SCN8A	ENST00000599343.5	c.3853-1106T>C		intron_variant		5		ENSP00000476447.3
SCN8A	ENST00000355133.7	c.3819+5181T>C		intron_variant		1		ENSP00000347255.4

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18959 AN: 152006 Hom.: 1455 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0840

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.125 AC: 18958 AN: 152124 Hom.: 1451 Cov.: 32 AF XY: 0.132 AC XY: 9818 AN XY: 74354

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.115

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.365

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.0840

Gnomad4 OTH AF: 0.108

Alfa AF: 0.0938 Hom.: 673

Bravo AF: 0.124

Asia WGS AF: 0.261 AC: 905 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.2
DANN	Benign	0.69

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: rs17126078; hg19: chr12-52173327;