rs200405157
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM1BP4_ModerateBS2
The NM_000116.5(TAFAZZIN):c.331C>T(p.His111Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000628 in 1,211,097 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 25 hemizygotes in GnomAD. 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_000116.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TAFAZZIN | NM_000116.5 | c.331C>T | p.His111Tyr | missense_variant | 4/11 | ENST00000601016.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TAFAZZIN | ENST00000601016.6 | c.331C>T | p.His111Tyr | missense_variant | 4/11 | 1 | NM_000116.5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000177 AC: 2AN: 112929Hom.: 0 Cov.: 24 AF XY: 0.0000285 AC XY: 1AN XY: 35079
GnomAD3 exomes AF: 0.0000273 AC: 5AN: 183323Hom.: 0 AF XY: 0.0000147 AC XY: 1AN XY: 67837
GnomAD4 exome AF: 0.0000674 AC: 74AN: 1098168Hom.: 0 Cov.: 31 AF XY: 0.0000660 AC XY: 24AN XY: 363542
GnomAD4 genome ? AF: 0.0000177 AC: 2AN: 112929Hom.: 0 Cov.: 24 AF XY: 0.0000285 AC XY: 1AN XY: 35079
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Sep 04, 2013 | The His111Tyr variant in TAZ has not been reported in any other families with ca rdiomyopathy, but has been identified in 1/6728 European American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs 200405157). Computational analyses (biochemical amino acid properties, conservat ion, AlignGVGD, PolyPhen2, and SIFT) suggest that the His111Tyr variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. Additional studies are needed to fully assess the clinical sign ificance of the His111Tyr variant. - |
3-Methylglutaconic aciduria type 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 10, 2022 | This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 111 of the TAZ protein (p.His111Tyr). This variant is present in population databases (rs200405157, gnomAD 0.008%). This missense change has been observed in individual(s) with left ventricular noncompaction cardiomyopathy (PMID: 33500567). ClinVar contains an entry for this variant (Variation ID: 165328). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). 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. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 27, 2022 | The p.H111Y variant (also known as c.331C>T), located in coding exon 4 of the TAZ gene, results from a C to T substitution at nucleotide position 331. The histidine at codon 111 is replaced by tyrosine, an amino acid with similar properties. This alteration has been reported in left ventricular non-compaction (LVNC) cohorts; however, clinical details were limited (Richard P et al. Clin Genet, 2019 03;95:356-367; Mazzarotto F et al. Genet Med, 2021 05;23:856-864). Based on data from gnomAD, the T allele has an overall frequency of 0.0029% (6/205368) total alleles studied, with 1 hemizygote(s) observed. The highest observed frequency was 0.0065% (6/92637) of European (non-Finnish) alleles. This amino acid position is poorly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 13, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at