rs72471101

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PM4_SupportingBP6_Very_StrongBA1

The NM_006922.4(SCN3A):c.127_129delAAT(p.Asn43del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0899 in 1,613,962 control chromosomes in the GnomAD database, including 7,425 homozygotes. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. N43N) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.083 ( 641 hom., cov: 31)

Exomes 𝑓: 0.091 ( 6784 hom. )

Consequence

SCN3A
NM_006922.4 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.78

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 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

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 -15 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_006922.4. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 2-165176265-CATT-C is Benign according to our data. Variant chr2-165176265-CATT-C is described in ClinVar as Benign. ClinVar VariationId is 95444.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0945 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN3A	NM_006922.4 link	c.127_129delAAT	p.Asn43del	conservative_inframe_deletion	Exon 3 of 28	ENST00000283254.12	NP_008853.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN3A	ENST00000283254.12 link	c.127_129delAAT	p.Asn43del	conservative_inframe_deletion	Exon 3 of 28	1	NM_006922.4	ENSP00000283254.7

Frequencies

GnomAD3 genomes

AF:

0.0831

AC:

12627

AN:

152024

Hom.:

641

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0590

Gnomad AMI

AF:

0.174

Gnomad AMR

AF:

0.0402

Gnomad ASJ

AF:

0.107

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.0782

Gnomad FIN

AF:

0.182

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0964

Gnomad OTH

AF:

0.0727

GnomAD2 exomes

AF:

0.0840

AC:

21119

AN:

251438

AF XY:

0.0873

show subpopulations

Gnomad AFR exome

AF:

0.0559

Gnomad AMR exome

AF:

0.0323

Gnomad ASJ exome

AF:

0.116

Gnomad EAS exome

AF:

0.00120

Gnomad FIN exome

AF:

0.178

Gnomad NFE exome

AF:

0.0965

Gnomad OTH exome

AF:

0.0872

GnomAD4 exome

AF:

0.0906

AC:

132502

AN:

1461820

Hom.:

6784

AF XY:

0.0911

AC XY:

66228

AN XY:

727214

show subpopulations

African (AFR)

AF:

0.0591

AC:

1978

AN:

33480

American (AMR)

AF:

0.0323

AC:

1446

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.111

AC:

2907

AN:

26136

East Asian (EAS)

AF:

0.000579

AC:

AN:

39698

South Asian (SAS)

AF:

0.0856

AC:

7386

AN:

86256

European-Finnish (FIN)

AF:

0.178

AC:

9499

AN:

53420

Middle Eastern (MID)

AF:

0.0843

AC:

486

AN:

5768

European-Non Finnish (NFE)

AF:

0.0930

AC:

103413

AN:

1111946

Other (OTH)

AF:

0.0888

AC:

5364

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

7177

14354

21532

28709

35886

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3688

7376

11064

14752

18440

<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:

0.0831

AC:

12636

AN:

152142

Hom.:

641

Cov.:

AF XY:

0.0850

AC XY:

6324

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.0591

AC:

2453

AN:

41522

American (AMR)

AF:

0.0402

AC:

614

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.107

AC:

370

AN:

3464

East Asian (EAS)

AF:

0.00212

AC:

AN:

5180

South Asian (SAS)

AF:

0.0783

AC:

377

AN:

4814

European-Finnish (FIN)

AF:

0.182

AC:

1922

AN:

10554

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0964

AC:

6556

AN:

68002

Other (OTH)

AF:

0.0715

AC:

151

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

566

1131

1697

2262

2828

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

146

292

438

584

730

<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:

0.0994

Hom.:

157

Bravo

AF:

0.0707

Asia WGS

AF:

0.0350

AC:

122

AN:

3478

EpiCase

AF:

0.0901

EpiControl

AF:

0.0888

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Apr 20, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 09, 2022

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

See Variant Classification Assertion Criteria. -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

May 09, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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 v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.8

Mutation Taster

=66/34

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over