Genetic Variant SCN4A:c.*1394_*1403dupATATATGTGT (chr17-63939367-C-CACACATATAT) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000334.4(SCN4A):c.*1394_*1403dupATATATGTGT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 15906 hom., cov: 0)

Exomes 𝑓: 0.13 ( 2 hom. )

Consequence

SCN4A
NM_000334.4 3_prime_UTR

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 0.130

Variant links:

Genes affected

SCN4A (HGNC:10591): (sodium voltage-gated channel alpha subunit 4) 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. It is expressed in skeletal muscle, and mutations in this gene have been linked to several myotonia and periodic paralysis disorders. [provided by RefSeq, Jul 2008]

SCN4A links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 17-63939367-C-CACACATATAT is Benign according to our data. Variant chr17-63939367-C-CACACATATAT is described in ClinVar as [Benign]. Clinvar id is 324479.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN4A	NM_000334.4 link	c.1394_1403dupATATATGTGT		3_prime_UTR_variant	Exon 24 of 24	ENST00000435607.3	NP_000325.4	P35499

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN4A	ENST00000435607.3 link	c.1394_1403dupATATATGTGT		3_prime_UTR_variant	Exon 24 of 24	1	NM_000334.4	ENSP00000396320.1		P35499

Frequencies

GnomAD3 genomes

AF:

0.431

AC:

65261

AN:

151246

Hom.:

15902

Cov.:

show subpopulations

Gnomad AFR

AF:

0.191

Gnomad AMI

AF:

0.602

Gnomad AMR

AF:

0.440

Gnomad ASJ

AF:

0.557

Gnomad EAS

AF:

0.456

Gnomad SAS

AF:

0.385

Gnomad FIN

AF:

0.523

Gnomad MID

AF:

0.567

Gnomad NFE

AF:

0.553

Gnomad OTH

AF:

0.474

GnomAD4 exome

AF:

0.132

AC:

AN:

Hom.:

Cov.:

AF XY:

0.113

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.250

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.148

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.431

AC:

65289

AN:

151362

Hom.:

15906

Cov.:

AF XY:

0.429

AC XY:

31701

AN XY:

73896

show subpopulations

African (AFR)

AF:

0.192

AC:

7932

AN:

41388

American (AMR)

AF:

0.440

AC:

6683

AN:

15204

Ashkenazi Jewish (ASJ)

AF:

0.557

AC:

1926

AN:

3458

East Asian (EAS)

AF:

0.456

AC:

2316

AN:

5084

South Asian (SAS)

AF:

0.385

AC:

1845

AN:

4790

European-Finnish (FIN)

AF:

0.523

AC:

5460

AN:

10434

Middle Eastern (MID)

AF:

0.552

AC:

160

AN:

290

European-Non Finnish (NFE)

AF:

0.553

AC:

37431

AN:

67724

Other (OTH)

AF:

0.476

AC:

999

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1647

3294

4941

6588

8235

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.294

Hom.:

684

Asia WGS

AF:

0.400

AC:

1395

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hypokalemic periodic paralysis

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Paramyotonia congenita of Von Eulenburg

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Congenital Myasthenic Syndrome, Recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

May 15, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Familial hyperkalemic periodic paralysis

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Potassium-aggravated myotonia

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.13

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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17-63939367-C-CACACATATAT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over