rs201552497
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_000334.4(SCN4A):c.483-9C>T 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 0.000229 in 1,503,966 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 Benign (★).
Frequency
Genomes: 𝑓 0.00016 ( 0 hom., cov: 30)
Exomes 𝑓: 0.00024 ( 3 hom. )
Consequence
SCN4A
NM_000334.4 splice_polypyrimidine_tract, intron
NM_000334.4 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.000008939
2
Clinical Significance
Conservation
PhyloP100: -0.152
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 17-63971859-G-A is Benign according to our data. Variant chr17-63971859-G-A is described in ClinVar as [Benign]. Clinvar id is 758817.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000158 (19/120524) while in subpopulation SAS AF= 0.00516 (19/3682). AF 95% confidence interval is 0.00338. There are 0 homozygotes in gnomad4. There are 15 alleles in male gnomad4 subpopulation. Median coverage is 30. 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.483-9C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000435607.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN4A | ENST00000435607.3 | c.483-9C>T | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000334.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000158 AC: 19AN: 120402Hom.: 0 Cov.: 30
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GnomAD3 exomes AF: 0.000483 AC: 115AN: 238328Hom.: 0 AF XY: 0.000656 AC XY: 85AN XY: 129568
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GnomAD4 exome AF: 0.000236 AC: 326AN: 1383442Hom.: 3 Cov.: 33 AF XY: 0.000336 AC XY: 230AN XY: 684624
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GnomAD4 genome ? AF: 0.000158 AC: 19AN: 120524Hom.: 0 Cov.: 30 AF XY: 0.000252 AC XY: 15AN XY: 59608
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hyperkalemic periodic paralysis Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 04, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at