rs145220602

Variant names:

• chr2-165090156-T-C
• rs145220602
• NM_006922.4:c.5997A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-165090156-T-C
• chr2-165090156-T-G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_006922.4(SCN3A):​c.5997A>G​(p.Gln1999Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000701 in 1,425,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: SCN3A NM_006922.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.73
• 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, STRONG Submitted by: Illumina, ClinGen, PanelApp Australia
• 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 2-165090156-T-C is Benign according to our data. Variant chr2-165090156-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3728218.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.73 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN3A	NM_006922.4	MANE Select	c.5997A>G	p.Gln1999Gln	synonymous	Exon 28 of 28	NP_008853.3
	SCN3A	NM_001081676.2		c.5850A>G	p.Gln1950Gln	synonymous	Exon 28 of 28	NP_001075145.1	Q9NY46-4
	SCN3A	NM_001081677.2		c.5850A>G	p.Gln1950Gln	synonymous	Exon 28 of 28	NP_001075146.1	Q9NY46-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN3A	ENST00000283254.12	TSL:1 MANE Select	c.5997A>G	p.Gln1999Gln	synonymous	Exon 28 of 28	ENSP00000283254.7	Q9NY46-3
	SCN3A	ENST00000409101.7	TSL:1	c.5850A>G	p.Gln1950Gln	synonymous	Exon 28 of 28	ENSP00000386726.3	Q9NY46-2
	SCN3A	ENST00000706067.1		c.5946A>G	p.Gln1982Gln	synonymous	Exon 28 of 28	ENSP00000516211.1	A0A994J5P2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.01e-7 AC: 1 AN: 1425928 Hom.: 0 Cov.: 29 AF XY: 0.00000142 AC XY: 1 AN XY: 706308

African (AFR) AF: 0.00 AC: 0 AN: 33136

American (AMR) AF: 0.00 AC: 0 AN: 39050

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25794

East Asian (EAS) AF: 0.0000256 AC: 1 AN: 39058

South Asian (SAS) AF: 0.00 AC: 0 AN: 83048

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51644

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5344

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1089886

Other (OTH) AF: 0.00 AC: 0 AN: 58968

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	4.0
DANN	Benign	0.88
PhyloP100		1.7
Mutation Taster		=100/0	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: rs145220602; hg19: chr2-165946666;