rs113659925

Variant names:

• chr11-118144025-G-A
• rs113659925
• NM_174934.4:c.271C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-118144025-G-A
• chr11-118144025-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_174934.4(SCN4B):​c.271C>T​(p.Pro91Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCN4B NM_174934.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.21

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN4B	NM_174934.4	c.271C>T	p.Pro91Ser	missense_variant	Exon 3 of 5	ENST00000324727.9	NP_777594.1
SCN4B	NM_001142349.2	c.-60C>T		5_prime_UTR_variant	Exon 2 of 4		NP_001135821.1
SCN4B	NM_001142348.2	c.62-2689C>T		intron_variant	Intron 1 of 2		NP_001135820.1
SCN4B	NR_024527.2	n.414C>T		non_coding_transcript_exon_variant	Exon 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN4B	ENST00000324727.9	c.271C>T	p.Pro91Ser	missense_variant	Exon 3 of 5	1	NM_174934.4	ENSP00000322460.4
SCN4B	ENST00000415030.6	n.414C>T		non_coding_transcript_exon_variant	Exon 2 of 4	1
SCN4B	ENST00000529878.1	c.62-2689C>T		intron_variant	Intron 1 of 2	4		ENSP00000436343.1
SCN4B	ENST00000532138.1	n.681C>T		non_coding_transcript_exon_variant	Exon 2 of 3	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cardiovascular phenotype Uncertain:1

Dec 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.271C>T (p.P91S) alteration is located in exon 3 (coding exon 3) of the SCN4B gene. This alteration results from a C to T substitution at nucleotide position 271, causing the proline (P) at amino acid position 91 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Benign	-0.00036	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.55	D
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.80	T
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-0.32	T
MutationAssessor	Pathogenic	3.0	M
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-4.8	D
REVEL	Uncertain	0.38
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.012	D
Polyphen		1.0	D
Vest4		0.54
MutPred		0.44		Loss of stability (P = 0.0523);
MVP		0.32
MPC		0.62
ClinPred		1.0	D
GERP RS		3.9
Varity_R		0.60
gMVP		0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs113659925; hg19: chr11-118014740;