rs672601319

Variant names:

• chr12-51688810-A-C
• NM_014191.4:c.667A>C

Your query was ambiguous. Multiple possible variants found:

• chr12-51688810-A-C
• chr12-51688810-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014191.4(SCN8A):​c.667A>C​(p.Arg223Arg) variant causes a synonymous change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,626 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SCN8A NM_014191.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.29

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN8A	NM_014191.4	c.667A>C	p.Arg223Arg	synonymous_variant	Exon 6 of 27	ENST00000354534.11	NP_055006.1
SCN8A	NM_001330260.2	c.615-195A>C		intron_variant	Intron 5 of 26	ENST00000627620.5	NP_001317189.1
SCN8A	NM_001177984.3	c.667A>C	p.Arg223Arg	synonymous_variant	Exon 6 of 26		NP_001171455.1
SCN8A	NM_001369788.1	c.615-195A>C		intron_variant	Intron 5 of 25		NP_001356717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN8A	ENST00000354534.11	c.667A>C	p.Arg223Arg	synonymous_variant	Exon 6 of 27	1	NM_014191.4	ENSP00000346534.4
SCN8A	ENST00000599343.5	c.667A>C	p.Arg223Arg	synonymous_variant	Exon 5 of 26	5		ENSP00000476447.3
SCN8A	ENST00000355133.7	c.667A>C	p.Arg223Arg	synonymous_variant	Exon 5 of 25	1		ENSP00000347255.4
SCN8A	ENST00000627620.5	c.615-195A>C		intron_variant	Intron 5 of 26	5	NM_001330260.2	ENSP00000487583.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461626 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727094

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	22
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-52082594;