rs62508752
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PM5PP3_Strong
The NM_000277.3(PAH):c.796A>G(p.Thr266Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. T266P) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000277.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PAH | NM_000277.3 | c.796A>G | p.Thr266Ala | missense_variant | 7/13 | ENST00000553106.6 | |
PAH | NM_001354304.2 | c.796A>G | p.Thr266Ala | missense_variant | 8/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PAH | ENST00000553106.6 | c.796A>G | p.Thr266Ala | missense_variant | 7/13 | 1 | NM_000277.3 | P1 | |
PAH | ENST00000307000.7 | c.781A>G | p.Thr261Ala | missense_variant | 8/14 | 5 | |||
PAH | ENST00000549247.6 | n.555A>G | non_coding_transcript_exon_variant | 1/6 | 2 | ||||
PAH | ENST00000635477.1 | upstream_gene_variant | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Phenylketonuria Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 28, 2021 | - - |
not provided Other:1
not provided, no classification provided | literature only | DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at