chr17-63941725-G-C
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_Strong
The NM_000334.4(SCN4A):āc.4557C>Gā(p.Phe1519Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,892 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 Uncertain significance (ā ). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F1519I) has been classified as Uncertain significance.
Frequency
Consequence
NM_000334.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN4A | NM_000334.4 | c.4557C>G | p.Phe1519Leu | missense_variant | 24/24 | ENST00000435607.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN4A | ENST00000435607.3 | c.4557C>G | p.Phe1519Leu | missense_variant | 24/24 | 1 | NM_000334.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250784Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135776
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461892Hom.: 0 Cov.: 35 AF XY: 0.00000275 AC XY: 2AN XY: 727246
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 21, 2022 | The c.4557C>G (p.F1519L) alteration is located in exon 24 (coding exon 24) of the SCN4A gene. This alteration results from a C to G substitution at nucleotide position 4557, causing the phenylalanine (F) at amino acid position 1519 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at