2-165164383-G-A

Variant names:

• chr2-165164383-G-A
• rs7579000
• NM_006922.4:c.602+9C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006922.4(SCN3A):​c.602+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 1,613,110 control chromosomes in the GnomAD database, including 26,558 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (5076 hom., cov: 32)
  • Exomes 𝑓: 0.15 (21482 hom.)
• Consequence: SCN3A NM_006922.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.134
• Publications: 8 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 2-165164383-G-A is Benign according to our data. Variant chr2-165164383-G-A is described in ClinVar as Benign. ClinVar VariationId is 586504.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006922.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN3A	NM_006922.4	MANE Select	c.602+9C>T		intron	N/A	NP_008853.3
	SCN3A	NM_001081676.2		c.602+9C>T		intron	N/A	NP_001075145.1
	SCN3A	NM_001081677.2		c.602+9C>T		intron	N/A	NP_001075146.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN3A	ENST00000283254.12	TSL:1 MANE Select	c.602+9C>T		intron	N/A	ENSP00000283254.7
	SCN3A	ENST00000409101.7	TSL:1	c.602+9C>T		intron	N/A	ENSP00000386726.3
	SCN3A	ENST00000706067.1		c.602+9C>T		intron	N/A	ENSP00000516211.1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34267 AN: 151794 Hom.: 5051 Cov.: 32

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.521

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.218

GnomAD2 exomes AF: 0.219 AC: 54929 AN: 251052 AF XY: 0.205

Gnomad AFR exome AF: 0.370

Gnomad AMR exome AF: 0.373

Gnomad ASJ exome AF: 0.134

Gnomad EAS exome AF: 0.535

Gnomad FIN exome AF: 0.228

Gnomad NFE exome AF: 0.116

Gnomad OTH exome AF: 0.182

GnomAD4 exome AF: 0.146 AC: 213102 AN: 1461198 Hom.: 21482 Cov.: 33 AF XY: 0.145 AC XY: 105536 AN XY: 726914

African (AFR) AF: 0.369 AC: 12350 AN: 33444

American (AMR) AF: 0.359 AC: 16027 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 3389 AN: 26110

East Asian (EAS) AF: 0.484 AC: 19156 AN: 39608

South Asian (SAS) AF: 0.186 AC: 16075 AN: 86242

European-Finnish (FIN) AF: 0.227 AC: 12118 AN: 53408

Middle Eastern (MID) AF: 0.128 AC: 738 AN: 5764

European-Non Finnish (NFE) AF: 0.110 AC: 122621 AN: 1111574

Other (OTH) AF: 0.176 AC: 10628 AN: 60368

GnomAD4 genome AF: 0.226 AC: 34339 AN: 151912 Hom.: 5076 Cov.: 32 AF XY: 0.232 AC XY: 17252 AN XY: 74218

African (AFR) AF: 0.361 AC: 14942 AN: 41414

American (AMR) AF: 0.287 AC: 4370 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 452 AN: 3468

East Asian (EAS) AF: 0.521 AC: 2677 AN: 5138

South Asian (SAS) AF: 0.191 AC: 917 AN: 4812

European-Finnish (FIN) AF: 0.232 AC: 2448 AN: 10548

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7846 AN: 67966

Other (OTH) AF: 0.228 AC: 481 AN: 2110

Alfa AF: 0.153 Hom.: 7901

Bravo AF: 0.242

Asia WGS AF: 0.370 AC: 1282 AN: 3478

EpiCase AF: 0.108

EpiControl AF: 0.105

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

May 15, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Apr 20, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 35% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 33. Only high quality variants are reported.

Epilepsy, familial focal, with variable foci 4 Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Developmental and epileptic encephalopathy, 62 Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
DANN	Benign	0.75
PhyloP100		0.13
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: rs7579000; hg19: chr2-166020893; COSMIC: COSV51810245; COSMIC: COSV51810245;