rs12424271

Variant names:

• chr12-51621184-G-A
• rs12424271
• NM_001330260.2:c.-55+29825G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-51621184-G-A
• chr12-51621184-G-C
• chr12-51621184-G-T

Variant summary

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

The NM_001330260.2(SCN8A):​c.-55+29825G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 152,062 control chromosomes in the GnomAD database, including 5,744 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 0.24 (5744 hom., cov: 32)
• Consequence: SCN8A NM_001330260.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN8A	NM_001330260.2	c.-55+29825G>A		intron_variant	Intron 1 of 26	ENST00000627620.5	NP_001317189.1
SCN8A	NM_014191.4	c.-55+29825G>A		intron_variant	Intron 1 of 26	ENST00000354534.11	NP_055006.1
SCN8A	NM_001177984.3	c.-55+29825G>A		intron_variant	Intron 1 of 25		NP_001171455.1
SCN8A	NM_001369788.1	c.-55+29825G>A		intron_variant	Intron 1 of 25		NP_001356717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN8A	ENST00000354534.11	c.-55+29825G>A		intron_variant	Intron 1 of 26	1	NM_014191.4	ENSP00000346534.4
SCN8A	ENST00000627620.5	c.-55+29825G>A		intron_variant	Intron 1 of 26	5	NM_001330260.2	ENSP00000487583.2

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35743 AN: 151944 Hom.: 5704 Cov.: 32

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.236 AC: 35843 AN: 152062 Hom.: 5744 Cov.: 32 AF XY: 0.238 AC XY: 17703 AN XY: 74318

Gnomad4 AFR AF: 0.435

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.146

Gnomad4 EAS AF: 0.323

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.221

Alfa AF: 0.129 Hom.: 814

Bravo AF: 0.243

Asia WGS AF: 0.393 AC: 1367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.049
DANN	Benign	0.46

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: rs12424271; hg19: chr12-52014968;