17-63939080-G-GCA

Variant summary

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

The NM_000334.4(SCN4A):c.*1690_*1691insTG 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.107

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 17-63939080-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/exons	MANE	UniProt
SCN4A	NM_000334.4	c.*1690_*1691insTG		3_prime_UTR_variant	24/24	ENST00000435607.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCN4A	ENST00000435607.3	c.*1690_*1691insTG		3_prime_UTR_variant	24/24	1	NM_000334.4	P1

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105488 AN: 151640 Hom.: 37827 Cov.: 0

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.: 67 Cov.: 0 AF XY: 0.574 AC XY: 155 AN XY: 270

Gnomad4 AMR exome AF: 0.00

Gnomad4 FIN exome AF: 0.556

Gnomad4 NFE exome AF: 0.423

Gnomad4 OTH exome AF: 0.350

GnomAD4 genome AF: 0.696 AC: 105587 AN: 151754 Hom.: 37878 Cov.: 0 AF XY: 0.684 AC XY: 50723 AN XY: 74156

Gnomad4 AFR AF: 0.874

Gnomad4 AMR AF: 0.578

Gnomad4 ASJ AF: 0.658

Gnomad4 EAS AF: 0.459

Gnomad4 SAS AF: 0.442

Gnomad4 FIN AF: 0.582

Gnomad4 NFE AF: 0.668

Gnomad4 OTH AF: 0.686

Asia WGS AF: 0.476 AC: 1660 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 14, 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: rs66908473; hg19: chr17-62016440;