12-21437752-C-G
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_024854.5(PYROXD1):āc.22C>Gā(p.Pro8Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,612,968 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_024854.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PYROXD1 | NM_024854.5 | c.22C>G | p.Pro8Ala | missense_variant | 1/12 | ENST00000240651.14 | |
PYROXD1 | XM_047429554.1 | c.22C>G | p.Pro8Ala | missense_variant | 1/10 | ||
PYROXD1 | XM_006719153.4 | c.22C>G | p.Pro8Ala | missense_variant | 1/8 | ||
PYROXD1 | NM_001350913.2 | c.-682C>G | 5_prime_UTR_variant | 1/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PYROXD1 | ENST00000240651.14 | c.22C>G | p.Pro8Ala | missense_variant | 1/12 | 1 | NM_024854.5 | P1 | |
PYROXD1 | ENST00000544970.5 | c.22C>G | p.Pro8Ala | missense_variant, NMD_transcript_variant | 1/11 | 1 | |||
PYROXD1 | ENST00000543476.5 | c.22C>G | p.Pro8Ala | missense_variant, NMD_transcript_variant | 1/9 | 5 | |||
PYROXD1 | ENST00000375266.8 | c.22C>G | p.Pro8Ala | missense_variant, NMD_transcript_variant | 1/13 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000525 AC: 8AN: 152238Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000205 AC: 5AN: 244188Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 132864
GnomAD4 exome AF: 0.0000164 AC: 24AN: 1460730Hom.: 0 Cov.: 33 AF XY: 0.0000165 AC XY: 12AN XY: 726544
GnomAD4 genome AF: 0.0000525 AC: 8AN: 152238Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74372
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 10, 2022 | This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 8 of the PYROXD1 protein (p.Pro8Ala). This variant is present in population databases (rs370239493, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with PYROXD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1409544). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 03, 2024 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at