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. The variant received 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P91H) has been classified 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
• Publications: 0 publications found

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]

SCN4B Gene-Disease associations (from GenCC):

• familial atrial fibrillation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• long QT syndrome 10

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
• long QT syndrome

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174934.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN4B	NM_174934.4	MANE Select	c.271C>T	p.Pro91Ser	missense	Exon 3 of 5	NP_777594.1	Q8IWT1-1
	SCN4B	NM_001142349.2		c.-60C>T		5_prime_UTR	Exon 2 of 4	NP_001135821.1	Q8IWT1-2
	SCN4B	NM_001142348.2		c.62-2689C>T		intron	N/A	NP_001135820.1	Q8IWT1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN4B	ENST00000324727.9	TSL:1 MANE Select	c.271C>T	p.Pro91Ser	missense	Exon 3 of 5	ENSP00000322460.4	Q8IWT1-1
	SCN4B	ENST00000415030.6	TSL:1	n.414C>T		non_coding_transcript_exon	Exon 2 of 4
	SCN4B	ENST00000529878.1	TSL:4	c.62-2689C>T		intron	N/A	ENSP00000436343.1	Q8IWT1-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Cardiovascular phenotype (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		5.2
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
Mutation Taster		=69/31	polymorphism

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

Other links and lift over

dbSNP: rs113659925; hg19: chr11-118014740;