rs7579000

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.134

Publications

8 publications found

Variant links:

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

SCN3A links:

ENSG00000236283 (HGNC:):

ENSG00000236283 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	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	Q9NY46-4
SCN3A	NM_001081677.2		c.602+9C>T	intron	N/A	NP_001075146.1	Q9NY46-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SCN3A	ENST00000283254.12	TSL:1 MANE Select	c.602+9C>T	intron	N/A	ENSP00000283254.7	Q9NY46-3
SCN3A	ENST00000409101.7	TSL:1	c.602+9C>T	intron	N/A	ENSP00000386726.3	Q9NY46-2
SCN3A	ENST00000706067.1		c.602+9C>T	intron	N/A	ENSP00000516211.1	A0A994J5P2

Frequencies

GnomAD3 genomes

AF:

0.226

AC:

34267

AN:

151794

Hom.:

5051

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.145

AC XY:

105536

AN XY:

726914

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

8902

17803

26705

35606

44508

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4892

9784

14676

19568

24460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.226

AC:

34339

AN:

151912

Hom.:

5076

Cov.:

AF XY:

0.232

AC XY:

17252

AN XY:

74218

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.115

AC:

7846

AN:

67966

Other (OTH)

AF:

0.228

AC:

481

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1238

2477

3715

4954

6192

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

334

668

1002

1336

1670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

Developmental and epileptic encephalopathy, 62 (1)

Epilepsy, familial focal, with variable foci 4 (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

(source)

DANN

Benign

0.75

PhyloP100

0.13

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over