11-118137107-C-G

Variant names:

• chr11-118137107-C-G
• NM_174934.4:c.607G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_174934.4(SCN4B):​c.607G>C​(p.Val203Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,812 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: SCN4B NM_174934.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.28

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36225504).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN4B	NM_174934.4	c.607G>C	p.Val203Leu	missense_variant	Exon 5 of 5	ENST00000324727.9	NP_777594.1
SCN4B	NM_001142349.2	c.277G>C	p.Val93Leu	missense_variant	Exon 4 of 4		NP_001135821.1
SCN4B	NM_001142348.2	c.205G>C	p.Val69Leu	missense_variant	Exon 3 of 3		NP_001135820.1
SCN4B	NR_024527.2	n.596G>C		non_coding_transcript_exon_variant	Exon 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN4B	ENST00000324727.9	c.607G>C	p.Val203Leu	missense_variant	Exon 5 of 5	1	NM_174934.4	ENSP00000322460.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460812 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726810

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: 9.00e-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
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.39	T;.
Eigen	Benign	0.020
Eigen_PC	Benign	-0.016
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Pathogenic	0.37	D
MetaRNN	Benign	0.36	T;T
MetaSVM	Pathogenic	0.80	D
MutationAssessor	Uncertain	2.2	M;.
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.4	N;D
REVEL	Uncertain	0.47
Sift	Uncertain	0.014	D;D
Sift4G	Uncertain	0.024	D;D
Polyphen		1.0	D;.
Vest4		0.32
MutPred		0.19		Loss of catalytic residue at V203 (P = 0.0407);.;
MVP		0.83
MPC		0.30
ClinPred		0.85	D
GERP RS		3.5
Varity_R		0.16
gMVP		0.36

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-118007822;