17-63939367-C-CACACATATAT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000334.4(SCN4A):c.*1403_*1404insATATATGTGT 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.130

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
SCN4A	NM_000334.4	c.*1403_*1404insATATATGTGT		3_prime_UTR_variant	24/24	ENST00000435607.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCN4A	ENST00000435607.3	c.*1403_*1404insATATATGTGT		3_prime_UTR_variant	24/24	1	NM_000334.4	P1

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65261 AN: 151246 Hom.: 15902 Cov.: 0

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: 10 AN: 76 Hom.: 2 Cov.: 0 AF XY: 0.113 AC XY: 7 AN XY: 62

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.148

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.431 AC: 65289 AN: 151362 Hom.: 15906 Cov.: 0 AF XY: 0.429 AC XY: 31701 AN XY: 73896

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.440

Gnomad4 ASJ AF: 0.557

Gnomad4 EAS AF: 0.456

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.523

Gnomad4 NFE AF: 0.553

Gnomad4 OTH AF: 0.476

Asia WGS AF: 0.400 AC: 1395 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Hypokalemic periodic paralysis Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Paramyotonia congenita of Von Eulenburg Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Hyperkalemic periodic paralysis Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Congenital Myasthenic Syndrome, Recessive Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

- -

Potassium-aggravated myotonia Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs112489358; hg19: chr17-62016727;