chr11-118141304-T-G

Variant names:

• chr11-118141304-T-G
• rs587777560
• NM_174934.4:c.496A>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_174934.4(SCN4B):​c.496A>C​(p.Ile166Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: SCN4B NM_174934.4 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.24

Genes affected

SCN4B (HGNC:10592): (sodium voltage-gated channel beta subunit 4) The protein encoded by this gene is one of several sodium channel beta subunits. These subunits interact with voltage-gated alpha subunits to change sodium channel kinetics. The encoded transmembrane protein forms interchain disulfide bonds with SCN2A. Defects in this gene are a cause of long QT syndrome type 10 (LQT10). Three protein-coding and one non-coding transcript variant have been found for this gene.[provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 11-118141304-T-G is Pathogenic according to our data. Variant chr11-118141304-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 140601.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN4B	NM_174934.4	c.496A>C	p.Ile166Leu	missense_variant	Exon 4 of 5	ENST00000324727.9	NP_777594.1
SCN4B	NM_001142349.2	c.166A>C	p.Ile56Leu	missense_variant	Exon 3 of 4		NP_001135821.1
SCN4B	NM_001142348.2	c.94A>C	p.Ile32Leu	missense_variant	Exon 2 of 3		NP_001135820.1
SCN4B	NR_024527.2	n.485A>C		non_coding_transcript_exon_variant	Exon 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN4B	ENST00000324727.9	c.496A>C	p.Ile166Leu	missense_variant	Exon 4 of 5	1	NM_174934.4	ENSP00000322460.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Atrial fibrillation, familial, 17 Pathogenic:1

Jul 01, 2013

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.31
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.27	T;.
Eigen	Uncertain	0.20
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Pathogenic	0.32	D
MetaRNN	Uncertain	0.62	D;D
MetaSVM	Pathogenic	0.83	D
MutationAssessor	Uncertain	2.2	M;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.3	N;N
REVEL	Pathogenic	0.66
Sift	Benign	0.076	T;D
Sift4G	Uncertain	0.046	D;D
Polyphen		0.80	P;.
Vest4		0.85
MutPred		0.23		Loss of sheet (P = 0.302);.;
MVP		0.86
MPC		0.31
ClinPred		0.95	D
GERP RS		4.3
Varity_R		0.34
gMVP		0.59

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: rs587777560; hg19: chr11-118012019;