rs530640921
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_000334.4(SCN4A):c.2913G>A(p.Lys971=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000131 in 1,612,248 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00014 ( 3 hom. )
Consequence
SCN4A
NM_000334.4 synonymous
NM_000334.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.299
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 -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.26).
BP6
?
Variant 17-63949469-C-T is Benign according to our data. Variant chr17-63949469-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 543820.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.299 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0000591 (9/152282) while in subpopulation SAS AF= 0.00186 (9/4828). AF 95% confidence interval is 0.000972. There are 0 homozygotes in gnomad4. There are 8 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 3 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN4A | NM_000334.4 | c.2913G>A | p.Lys971= | synonymous_variant | 15/24 | ENST00000435607.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN4A | ENST00000435607.3 | c.2913G>A | p.Lys971= | synonymous_variant | 15/24 | 1 | NM_000334.4 | P1 | |
SCN4A | ENST00000584310.1 | n.236G>A | non_coding_transcript_exon_variant | 1/3 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000591 AC: 9AN: 152164Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000342 AC: 84AN: 245510Hom.: 2 AF XY: 0.000442 AC XY: 59AN XY: 133392
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GnomAD4 exome AF: 0.000138 AC: 202AN: 1459966Hom.: 3 Cov.: 31 AF XY: 0.000200 AC XY: 145AN XY: 726150
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GnomAD4 genome ? AF: 0.0000591 AC: 9AN: 152282Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8AN XY: 74452
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hyperkalemic periodic paralysis Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Aug 10, 2023 | - - |
Paramyotonia congenita of Von Eulenburg;C0238357:Hyperkalemic periodic paralysis;C2750061:Hypokalemic periodic paralysis, type 2;C2931826:Potassium-aggravated myotonia;C3280112:Congenital myasthenic syndrome 16;C3714580:Hypokalemic periodic paralysis, type 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Dec 02, 2021 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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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