17-63939080-G-GCA

Variant names:

Variant summary

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

The NM_000334.4(SCN4A):c.*1689_*1690dupTG 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 0.70 ( 37878 hom., cov: 0)

Exomes 𝑓: 0.54 ( 67 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: -0.107

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

hyperkalemic periodic paralysis
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, Orphanet
paramyotonia congenita of Von Eulenburg
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, Orphanet
SCN4A-related myopathy, autosomal recessive
Inheritance: AR Classification: DEFINITIVE Submitted by: Illumina, ClinGen
hypokalemic periodic paralysis, type 2
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
potassium-aggravated myotonia
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
congenital myasthenic syndrome 16
Inheritance: AR Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
congenital myopathy
Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
congenital myopathy 22A, classic
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
acetazolamide-responsive myotonia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hypokalemic periodic paralysis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
myotonia fluctuans
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
myotonia permanens
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
postsynaptic congenital myasthenic syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SCN4A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP6

Variant 17-63939080-G-GCA is Benign according to our data. Variant chr17-63939080-G-GCA is described in ClinVar as [Benign]. Clinvar id is 324474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN4A	NM_000334.4 link	c.1689_1690dupTG		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.1689_1690dupTG		3_prime_UTR_variant	Exon 24 of 24	1	NM_000334.4	ENSP00000396320.1		P35499

Frequencies

GnomAD3 genomes

AF:

0.696

AC:

105488

AN:

151640

Hom.:

37827

Cov.:

show subpopulations

Gnomad AFR

AF:

0.874

Gnomad AMI

AF:

0.773

Gnomad AMR

AF:

0.578

Gnomad ASJ

AF:

0.658

Gnomad EAS

AF:

0.460

Gnomad SAS

AF:

0.443

Gnomad FIN

AF:

0.582

Gnomad MID

AF:

0.775

Gnomad NFE

AF:

0.668

Gnomad OTH

AF:

0.687

GnomAD4 exome

AF:

0.537

AC:

247

AN:

460

Hom.:

Cov.:

AF XY:

0.574

AC XY:

155

AN XY:

270

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.556

AC:

229

AN:

412

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.423

AC:

AN:

Other (OTH)

AF:

0.350

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.696

AC:

105587

AN:

151754

Hom.:

37878

Cov.:

AF XY:

0.684

AC XY:

50723

AN XY:

74156

show subpopulations

African (AFR)

AF:

0.874

AC:

36106

AN:

41300

American (AMR)

AF:

0.578

AC:

8828

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.658

AC:

2279

AN:

3466

East Asian (EAS)

AF:

0.459

AC:

2372

AN:

5168

South Asian (SAS)

AF:

0.442

AC:

2128

AN:

4814

European-Finnish (FIN)

AF:

0.582

AC:

6127

AN:

10530

Middle Eastern (MID)

AF:

0.772

AC:

227

AN:

294

European-Non Finnish (NFE)

AF:

0.668

AC:

45367

AN:

67886

Other (OTH)

AF:

0.686

AC:

1448

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1566

3132

4697

6263

7829

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.519

Hom.:

979

Asia WGS

AF:

0.476

AC:

1660

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 14, 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

-0.11

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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17-63939080-G-GCA

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