rs1347992

Variant names:

• chr2-165105355-T-C
• rs1347992
• NM_006922.4:c.3844-4931A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-165105355-T-C
• chr2-165105355-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006922.4(SCN3A):​c.3844-4931A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,024 control chromosomes in the GnomAD database, including 3,626 homozygotes. 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: 𝑓 0.22 (3626 hom., cov: 32)
• Consequence: SCN3A NM_006922.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.621
• Publications: 6 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN3A	NM_006922.4	c.3844-4931A>G		intron_variant	Intron 21 of 27	ENST00000283254.12	NP_008853.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN3A	ENST00000283254.12	c.3844-4931A>G		intron_variant	Intron 21 of 27	1	NM_006922.4	ENSP00000283254.7

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33474 AN: 151906 Hom.: 3624 Cov.: 32

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.233

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.220 AC: 33489 AN: 152024 Hom.: 3626 Cov.: 32 AF XY: 0.219 AC XY: 16294 AN XY: 74300

African (AFR) AF: 0.204 AC: 8443 AN: 41460

American (AMR) AF: 0.226 AC: 3449 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 893 AN: 3468

East Asian (EAS) AF: 0.255 AC: 1318 AN: 5160

South Asian (SAS) AF: 0.273 AC: 1317 AN: 4822

European-Finnish (FIN) AF: 0.196 AC: 2073 AN: 10558

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.224 AC: 15215 AN: 67978

Other (OTH) AF: 0.229 AC: 484 AN: 2112

Alfa AF: 0.221 Hom.: 3224

Bravo AF: 0.221

Asia WGS AF: 0.253 AC: 881 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.92
DANN	Benign	0.52
PhyloP100		-0.62
Mutation Taster		=100/0	polymorphism (auto)

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: rs1347992; hg19: chr2-165961865;