rs786205425

Positions:

• chr11-123645589-G-T

Variant summary

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

The NM_001040151.2(SCN3B):​c.217C>A​(p.Leu73Ile) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCN3B NM_001040151.2 missense, splice_region
• Scores: Splicing: ADA: 0.9398
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.36

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36702913).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN3B	NM_001040151.2	c.217C>A	p.Leu73Ile	missense_variant, splice_region_variant	3/7	ENST00000299333.8	NP_001035241.1
SCN3B	NM_018400.4	c.217C>A	p.Leu73Ile	missense_variant, splice_region_variant	2/6		NP_060870.1
SCN3B	XM_011542897.3	c.217C>A	p.Leu73Ile	missense_variant, splice_region_variant	3/7		XP_011541199.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN3B	ENST00000299333.8	c.217C>A	p.Leu73Ile	missense_variant, splice_region_variant	3/7	1	NM_001040151.2	ENSP00000299333	P1

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

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

research

Biesecker Lab/Clinical Genomics Section, National Institutes of Health

Jun 24, 2013

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T;T;T;T;.
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.82	.;T;.;.;.
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.37	T;T;T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.3	L;L;L;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	0.19	N;N;N;N;N
REVEL	Benign	0.16
Sift	Benign	0.24	T;T;T;T;T
Sift4G	Benign	0.34	T;T;T;.;.
Polyphen		0.59	P;P;P;.;.
Vest4		0.45
MutPred		0.49		Gain of methylation at K70 (P = 0.0568);Gain of methylation at K70 (P = 0.0568);Gain of methylation at K70 (P = 0.0568);Gain of methylation at K70 (P = 0.0568);Gain of methylation at K70 (P = 0.0568);
MVP		0.54
MPC		0.85
ClinPred		0.90	D
GERP RS		6.0
Varity_R		0.23
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.94
dbscSNV1_RF	Pathogenic	0.80
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: rs786205425; hg19: chr11-123516297;