rs540296842
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PM5PP3
The NM_001257096.2(PAX1):c.497G>C(p.Gly166Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,612,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/20 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G166V) has been classified as Pathogenic.
Frequency
Consequence
NM_001257096.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PAX1 | NM_001257096.2 | c.497G>C | p.Gly166Ala | missense_variant | 2/5 | ENST00000613128.5 | |
PAX1 | NM_006192.5 | c.497G>C | p.Gly166Ala | missense_variant | 2/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PAX1 | ENST00000613128.5 | c.497G>C | p.Gly166Ala | missense_variant | 2/5 | 1 | NM_001257096.2 | P1 | |
PAX1 | ENST00000398485.6 | c.497G>C | p.Gly166Ala | missense_variant | 2/5 | 5 | |||
PAX1 | ENST00000444366.2 | c.425G>C | p.Gly142Ala | missense_variant | 1/4 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152226Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249290Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135160
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1459912Hom.: 0 Cov.: 31 AF XY: 0.00000826 AC XY: 6AN XY: 726390
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152344Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74486
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 23, 2020 | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at