rs1060500044
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PM1PM2PM5PP3_StrongPP5_Very_Strong
The NM_000116.5(TAFAZZIN):c.281G>A(p.Arg94His) variant causes a missense change. The variant allele was found at a frequency of 0.000000911 in 1,098,054 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R94S) has been classified as Pathogenic.
Frequency
Consequence
NM_000116.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TAFAZZIN | NM_000116.5 | c.281G>A | p.Arg94His | missense_variant | 3/11 | ENST00000601016.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TAFAZZIN | ENST00000601016.6 | c.281G>A | p.Arg94His | missense_variant | 3/11 | 1 | NM_000116.5 |
Frequencies
GnomAD3 genomes ? Cov.: 24
GnomAD4 exome AF: 9.11e-7 AC: 1AN: 1098054Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 363436
GnomAD4 genome ? Cov.: 24
ClinVar
Submissions by phenotype
not provided Pathogenic:3
Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2019 | - - |
Pathogenic, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Pathogenic, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
3-Methylglutaconic aciduria type 2 Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Molecular Diagnostics Lab, Nemours Children's Health, Delaware | Aug 18, 2020 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 08, 2023 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 94 of the TAZ protein (p.Arg94His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of TAZ-related conditions (PMID: 16548007, 23656970, 26724946). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 653322). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant disrupts the p.Arg94 amino acid residue in TAZ. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9345098, 12032589, 20812380, 26845103, 28123175). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at