rs2105615122

Variant names:

• chr2-165090170-C-A
• rs2105615122
• NM_006922.4:c.5983G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-165090170-C-A
• chr2-165090170-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006922.4(SCN3A):​c.5983G>T​(p.Val1995Phe) 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1995D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCN3A NM_006922.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.104
• Publications: 0 publications found

Genes affected

SCN3A (HGNC:10590): (sodium voltage-gated channel alpha subunit 3) Voltage-gated sodium channels are transmembrane glycoprotein complexes composed of a large alpha subunit with 24 transmembrane domains 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 alpha subunit gene family, and is found in a cluster of five alpha subunit genes on chromosome 2. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

SCN3A Gene-Disease associations (from GenCC):

• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: Illumina, ClinGen
• developmental and epileptic encephalopathy, 62

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• epilepsy, familial focal, with variable foci 4

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000236283 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09704304).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN3A	NM_006922.4	c.5983G>T	p.Val1995Phe	missense_variant	Exon 28 of 28	ENST00000283254.12	NP_008853.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN3A	ENST00000283254.12	c.5983G>T	p.Val1995Phe	missense_variant	Exon 28 of 28	1	NM_006922.4	ENSP00000283254.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Uncertain	0.076	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	18
DANN	Benign	0.90
DEOGEN2	Benign	0.32	T;.;.;.
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.025
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.66	T;T;T;T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.097	T;T;T;T
MetaSVM	Uncertain	0.73	D
MutationAssessor	Benign	0.34	N;N;.;.
PhyloP100		0.10
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.5	N;N;.;N
REVEL	Uncertain	0.33
Sift	Uncertain	0.019	D;D;.;D
Sift4G	Benign	0.70	T;T;.;T
Polyphen		0.31, 0.045	.;B;.;B
Vest4		0.18
MutPred		0.15		Loss of MoRF binding (P = 0.0854);Loss of MoRF binding (P = 0.0854);.;.;
MVP		0.23
MPC		1.0
ClinPred		0.16	T
GERP RS		6.0
Varity_R		0.15
gMVP		0.44
Mutation Taster		=54/46	polymorphism

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

Other links and lift over

dbSNP: rs2105615122; hg19: chr2-165946680;