rs116682517

chr2-165164442-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_006922.4(SCN3A):c.552G>A(p.Thr184=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,613,714 control chromosomes in the GnomAD database, including 157 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0085 (13 hom., cov: 32)
  • Exomes 𝑓: 0.012 (144 hom.)
• Consequence: SCN3A NM_006922.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.895

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 2-165164442-C-T is Benign according to our data. Variant chr2-165164442-C-T is described in ClinVar as [Benign]. Clinvar id is 240714.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.895 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00847 (1290/152218) while in subpopulation NFE AF= 0.0129 (875/68010). AF 95% confidence interval is 0.0122. There are 13 homozygotes in gnomad4. There are 570 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 1290 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCN3A	NM_006922.4	c.552G>A	p.Thr184=	synonymous_variant	6/28	ENST00000283254.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCN3A	ENST00000283254.12	c.552G>A	p.Thr184=	synonymous_variant	6/28	1	NM_006922.4	P1

Frequencies

GnomAD3 genomes AF: 0.00848 AC: 1290 AN: 152100 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.00222

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00754

Gnomad ASJ AF: 0.0228

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0104

Gnomad FIN AF: 0.00434

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0129

Gnomad OTH AF: 0.0148

GnomAD3 exomes AF: 0.0101 AC: 2538 AN: 251184 Hom.: 21 AF XY: 0.0105 AC XY: 1431 AN XY: 135780

Gnomad AFR exome AF: 0.00209

Gnomad AMR exome AF: 0.00475

Gnomad ASJ exome AF: 0.0205

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0110

Gnomad FIN exome AF: 0.00388

Gnomad NFE exome AF: 0.0145

Gnomad OTH exome AF: 0.0109

GnomAD4 exome AF: 0.0123 AC: 18027 AN: 1461496 Hom.: 144 Cov.: 32 AF XY: 0.0123 AC XY: 8975 AN XY: 727042

Gnomad4 AFR exome AF: 0.00209

Gnomad4 AMR exome AF: 0.00537

Gnomad4 ASJ exome AF: 0.0198

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0104

Gnomad4 FIN exome AF: 0.00567

Gnomad4 NFE exome AF: 0.0137

Gnomad4 OTH exome AF: 0.0113

GnomAD4 genome AF: 0.00847 AC: 1290 AN: 152218 Hom.: 13 Cov.: 32 AF XY: 0.00766 AC XY: 570 AN XY: 74426

Gnomad4 AFR AF: 0.00221

Gnomad4 AMR AF: 0.00753

Gnomad4 ASJ AF: 0.0228

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0104

Gnomad4 FIN AF: 0.00434

Gnomad4 NFE AF: 0.0129

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.0116 Hom.: 2

Bravo AF: 0.00842

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.0151

EpiControl AF: 0.0164

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Mar 21, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2024	SCN3A: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
Cadd	Benign	5.5
Dann	Benign	0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs116682517; hg19: chr2-166020952;