rs121908912
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM2PM5PP3_StrongPP5
The NM_001365536.1(SCN9A):c.3925G>T(p.Val1309Phe) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 14/23 in silico tools predict a damaging outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1309D) has been classified as Pathogenic.
Frequency
Consequence
NM_001365536.1 missense, splice_region
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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SCN9A | NM_001365536.1 | c.3925G>T | p.Val1309Phe | missense_variant, splice_region_variant | 22/27 | ENST00000642356.2 | |
SCN1A-AS1 | NR_110260.1 | n.612-19223C>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SCN9A | ENST00000642356.2 | c.3925G>T | p.Val1309Phe | missense_variant, splice_region_variant | 22/27 | NM_001365536.1 | P1 | ||
SCN1A-AS1 | ENST00000651574.1 | n.1290-19223C>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 6.88e-7 AC: 1AN: 1453624Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 722186
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Paroxysmal extreme pain disorder Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 07, 2006 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at