11-123634162-G-T

Variant names:

• chr11-123634162-G-T
• rs186341159
• NM_001040151.2:c.629C>A

Variant summary

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

The NM_001040151.2(SCN3B):​c.629C>A​(p.Ala210Glu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCN3B NM_001040151.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.714

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]

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
SCN3B	NM_001040151.2	c.629C>A	p.Ala210Glu	missense_variant	Exon 6 of 7	ENST00000299333.8	NP_001035241.1
SCN3B	NM_018400.4	c.629C>A	p.Ala210Glu	missense_variant	Exon 5 of 6		NP_060870.1
SCN3B	XM_011542897.3	c.629C>A	p.Ala210Glu	missense_variant	Exon 6 of 7		XP_011541199.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN3B	ENST00000299333.8	c.629C>A	p.Ala210Glu	missense_variant	Exon 6 of 7	1	NM_001040151.2	ENSP00000299333.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00000485 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	18
DANN	Benign	0.91
DEOGEN2	Uncertain	0.48	T;T;T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.81	.;T;.
M_CAP	Benign	0.069	D
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Uncertain	-0.10	T
MutationAssessor	Benign	1.4	L;L;L
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.5	N;N;N
REVEL	Uncertain	0.33
Sift	Uncertain	0.020	D;D;D
Sift4G	Benign	0.11	T;T;T
Polyphen		0.099	B;B;B
Vest4		0.30
MutPred		0.10		Gain of solvent accessibility (P = 0.0411);Gain of solvent accessibility (P = 0.0411);Gain of solvent accessibility (P = 0.0411);
MVP		0.68
MPC		0.57
ClinPred		0.33	T
GERP RS		0.80
Varity_R		0.13
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.45		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.45		Position offset: -41

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs186341159; hg19: chr11-123504870;