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. The variant received -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
• Publications: 2 publications found

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]

SCN8A Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, PanelApp Australia
• developmental and epileptic encephalopathy, 13

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
• cognitive impairment with or without cerebellar ataxia

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• seizures, benign familial infantile, 5

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• benign familial infantile epilepsy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• infantile convulsions and choreoathetosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• myoclonus, familial, 2

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330260.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN8A	NM_001330260.2	MANE Select	c.-55+29825G>A		intron	N/A	NP_001317189.1	Q9UQD0-2
	SCN8A	NM_014191.4	MANE Plus Clinical	c.-55+29825G>A		intron	N/A	NP_055006.1	Q9UQD0-1
	SCN8A	NM_001177984.3		c.-55+29825G>A		intron	N/A	NP_001171455.1	Q9UQD0-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN8A	ENST00000354534.11	TSL:1 MANE Plus Clinical	c.-55+29825G>A		intron	N/A	ENSP00000346534.4	Q9UQD0-1
	SCN8A	ENST00000627620.5	TSL:5 MANE Select	c.-55+29825G>A		intron	N/A	ENSP00000487583.2	Q9UQD0-2
	SCN8A	ENST00000546961.1	TSL:1	c.-55+30511G>A		intron	N/A	ENSP00000486828.1

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

African (AFR) AF: 0.435 AC: 18049 AN: 41454

American (AMR) AF: 0.208 AC: 3181 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 505 AN: 3470

East Asian (EAS) AF: 0.323 AC: 1671 AN: 5170

South Asian (SAS) AF: 0.297 AC: 1432 AN: 4818

European-Finnish (FIN) AF: 0.203 AC: 2136 AN: 10544

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8158 AN: 67990

Other (OTH) AF: 0.221 AC: 467 AN: 2116

Alfa AF: 0.133 Hom.: 978

Bravo AF: 0.243

Asia WGS AF: 0.393 AC: 1367 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.049
DANN	Benign	0.46
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12424271; hg19: chr12-52014968;