rs1555198495
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PP3_ModeratePP5
The NM_000317.3(PTS):āc.340A>Gā(p.Ile114Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,194 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).
Frequency
Consequence
NM_000317.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461194Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726822
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
6-Pyruvoyl-tetrahydrobiopterin synthase deficiency Pathogenic:2Uncertain:2
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Variant summary: PTS c.340A>G (p.Ile114Val) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 250116 control chromosomes (gnomAD). c.340A>G has been reported in the literature in homozygous individuals affected with 6-Pyruvoyl-Tetrahydropterin Synthase Deficiency, one of which had a milder form of the disease (Ashida_1994, Hanihara_1997). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 7698774, 9159737). ClinVar contains an entry for this variant (Variation ID: 558723). Based on the evidence outlined above, the variant was classified as likely pathogenic. -
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at