12-51806958-C-T

Position:

• chr12-51806958-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001330260.2(SCN8A):​c.5472C>T​(p.Pro1824Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P1824P) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCN8A NM_001330260.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570

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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP7: Synonymous conserved (PhyloP=-0.057 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN8A	NM_001330260.2	c.5472C>T	p.Pro1824Pro	synonymous_variant	27/27	ENST00000627620.5	NP_001317189.1
SCN8A	NM_014191.4	c.5472C>T	p.Pro1824Pro	synonymous_variant	27/27	ENST00000354534.11	NP_055006.1
SCN8A	NM_001177984.3	c.5349C>T	p.Pro1783Pro	synonymous_variant	26/26		NP_001171455.1
SCN8A	NM_001369788.1	c.5349C>T	p.Pro1783Pro	synonymous_variant	26/26		NP_001356717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN8A	ENST00000354534.11	c.5472C>T	p.Pro1824Pro	synonymous_variant	27/27	1	NM_014191.4	ENSP00000346534.4
SCN8A	ENST00000627620.5	c.5472C>T	p.Pro1824Pro	synonymous_variant	27/27	5	NM_001330260.2	ENSP00000487583.2
SCN8A	ENST00000599343.5	c.5505C>T	p.Pro1835Pro	synonymous_variant	26/26	5		ENSP00000476447.3
SCN8A	ENST00000355133.7	c.5349C>T	p.Pro1783Pro	synonymous_variant	25/25	1		ENSP00000347255.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 64

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	7.1
DANN	Benign	0.86

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: rs60637; hg19: chr12-52200742;