rs542836462
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_000334.4(SCN4A):c.612-17del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00292 in 403,824 control chromosomes in the GnomAD database, including 11 homozygotes. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0098 ( 8 hom., cov: 32)
Exomes 𝑓: 0.0014 ( 3 hom. )
Consequence
SCN4A
NM_000334.4 splice_polypyrimidine_tract, intron
NM_000334.4 splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.281
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
?
Variant 17-63971269-AG-A is Benign according to our data. Variant chr17-63971269-AG-A is described in ClinVar as [Benign]. Clinvar id is 255860.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00984 (698/70942) while in subpopulation AFR AF= 0.0346 (677/19590). AF 95% confidence interval is 0.0324. There are 8 homozygotes in gnomad4. There are 316 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 8 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN4A | NM_000334.4 | c.612-17del | splice_polypyrimidine_tract_variant, intron_variant | ENST00000435607.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN4A | ENST00000435607.3 | c.612-17del | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000334.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00983 AC: 697AN: 70908Hom.: 8 Cov.: 32
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GnomAD3 exomes AF: 0.00145 AC: 151AN: 104450Hom.: 0 AF XY: 0.00106 AC XY: 61AN XY: 57318
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GnomAD4 exome AF: 0.00145 AC: 482AN: 332882Hom.: 3 Cov.: 20 AF XY: 0.00110 AC XY: 193AN XY: 176226
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GnomAD4 genome ? AF: 0.00984 AC: 698AN: 70942Hom.: 8 Cov.: 32 AF XY: 0.00900 AC XY: 316AN XY: 35102
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 07, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 21, 2016 | - - |
Hyperkalemic periodic paralysis Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at