rs1557194203
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_000116.5(TAFAZZIN):c.680dup(p.Tyr227Ter) variant causes a stop gained, frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 23)
Consequence
TAFAZZIN
NM_000116.5 stop_gained, frameshift
NM_000116.5 stop_gained, frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.56
Genes affected
TAFAZZIN (HGNC:11577): (tafazzin, phospholipid-lysophospholipid transacylase) This gene encodes a protein that is expressed at high levels in cardiac and skeletal muscle. Mutations in this gene have been associated with a number of clinical disorders including Barth syndrome, dilated cardiomyopathy (DCM), hypertrophic DCM, endocardial fibroelastosis, and left ventricular noncompaction (LVNC). Multiple transcript variants encoding different isoforms have been described. A long form and a short form of each of these isoforms is produced; the short form lacks a hydrophobic leader sequence and may exist as a cytoplasmic protein rather than being membrane-bound. Other alternatively spliced transcripts have been described but the full-length nature of all these transcripts is not known. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TAFAZZIN | NM_000116.5 | c.680dup | p.Tyr227Ter | stop_gained, frameshift_variant | 9/11 | ENST00000601016.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TAFAZZIN | ENST00000601016.6 | c.680dup | p.Tyr227Ter | stop_gained, frameshift_variant | 9/11 | 1 | NM_000116.5 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 23
GnomAD4 genome
?
Cov.:
23
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Left ventricular noncompaction Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Institute Of Molecular Biology And Genetics, Federal Almazov National Medical Research Centre | - | The boy presented with muscle hypotonia and dilated cardiomyopathy in combination with left ventricular non-compaction and heart failure at 2 month old. Transient hyponeutrophilia was also observed. Similar genetic variant in TAZ gene was detected in patient's mother who is asymptomatic. Based on the clinical phenotype the probability of the variant to be causative is very high. However, according ton ACMG this variant currently is classified as VUS. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at