chr11-123653785-C-T

Position:

• chr11-123653785-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP5 BP4

The NM_001040151.2(SCN3B):​c.17G>A​(p.Arg6Lys) variant causes a missense 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SCN3B NM_001040151.2 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.14

Genes affected

SCN3B (HGNC:20665): (sodium voltage-gated channel beta subunit 3) Voltage-gated sodium channels are transmembrane glycoprotein complexes composed of a large alpha subunit and one or more regulatory beta subunits. They are responsible for the generation and propagation of action potentials in neurons and muscle. This gene encodes one member of the sodium channel beta subunit gene family, and influences the inactivation kinetics of the sodium channel. Two alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]

LOC105369543 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 11-123653785-C-T is Pathogenic according to our data. Variant chr11-123653785-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 140599.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.23738131). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN3B	NM_001040151.2	c.17G>A	p.Arg6Lys	missense_variant	2/7	ENST00000299333.8	NP_001035241.1
SCN3B	NM_018400.4	c.17G>A	p.Arg6Lys	missense_variant	1/6		NP_060870.1
SCN3B	XM_011542897.3	c.17G>A	p.Arg6Lys	missense_variant	2/7		XP_011541199.1
LOC105369543	XR_948124.4	n.101C>T		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN3B	ENST00000299333.8	c.17G>A	p.Arg6Lys	missense_variant	2/7	1	NM_001040151.2	ENSP00000299333.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Atrial fibrillation, familial, 16 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 01, 2011

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T;T;T;T;.
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.032
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.62	.;T;.;.;.
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.24	T;T;T;T;T
MetaSVM	Uncertain	0.48	D
MutationAssessor	Benign	1.4	L;L;L;.;.
MutationTaster	Benign	0.97	D;D;D
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.57	N;N;N;N;N
REVEL	Uncertain	0.48
Sift	Benign	0.40	T;T;T;T;T
Sift4G	Benign	1.0	T;T;T;.;.
Polyphen		0.0	B;B;B;.;.
Vest4		0.060
MutPred		0.46		Gain of methylation at R6 (P = 0.0162);Gain of methylation at R6 (P = 0.0162);Gain of methylation at R6 (P = 0.0162);Gain of methylation at R6 (P = 0.0162);Gain of methylation at R6 (P = 0.0162);
MVP		0.91
MPC		0.43
ClinPred		0.37	T
GERP RS		5.0
Varity_R		0.20
gMVP		0.69

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: rs587777558; hg19: chr11-123524493;