chr17-63964587-C-A
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM2PM5PP3_StrongPP5
The NM_000334.4(SCN4A):c.1333G>T(p.Val445Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,388 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V445M) has been classified as Pathogenic.
Frequency
Consequence
NM_000334.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SCN4A | NM_000334.4 | c.1333G>T | p.Val445Leu | missense_variant | Exon 9 of 24 | ENST00000435607.3 | NP_000325.4 | |
LOC105371858 | XR_001752969.2 | n.282C>A | non_coding_transcript_exon_variant | Exon 4 of 5 | ||||
LOC105371858 | XR_001752970.2 | n.337C>A | non_coding_transcript_exon_variant | Exon 4 of 5 | ||||
LOC105371858 | XR_934910.3 | n.157C>A | non_coding_transcript_exon_variant | Exon 3 of 4 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461388Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 726978
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Batten-Turner congenital myopathy Pathogenic:1
Likely pathogenic, no assertion criteria provided | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Jun 23, 2016 | - - |
Hyperkalemic periodic paralysis Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Jan 01, 2016 | This variant was classified as: Likely pathogenic. - |
Pain;C0030196:Limb pain;C0151786:Muscle weakness;C1847584:Distal sensory impairment;C4022169:EMG: myotonic discharges Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Jan 01, 2017 | - - |
Muscle weakness;C0700153:Myotonia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Jun 11, 2014 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at