rs397515749
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000116.5(TAFAZZIN):c.778-24_778-7delinsA variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 23)
Consequence
TAFAZZIN
NM_000116.5 splice_region, splice_polypyrimidine_tract, intron
NM_000116.5 splice_region, splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.638
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 Uncertain_significance. Variant got 2 ACMG points.
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.778-24_778-7delinsA | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000601016.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TAFAZZIN | ENST00000601016.6 | c.778-24_778-7delinsA | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000116.5 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD3 genomes
Cov.:
23
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
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
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 29, 2011 | Variant classified as Uncertain Significance - Favor Pathogenic. The 778-24_778- 7delinsA variant has not been reported in the literature and has not been previo usly detected in 369 Caucasian individuals tested by our laboratory. This varian t affects a region that is part of the splicing consensus sequence (-3 and -5 to -12) computational analyses predict that it affects splicing of exon 11. Howeve r, these tools are not predictive enough to assume pathogenicity and further mRN A studies are needed to confirm this. Pathogenic splice variants are common in t he TAZ gene (http://www.barthsyndrome.org) and the presence of a TAZ variant is consistent with this individual?s clinical presentation and family history. In summary, it is very likely that the 778-24_778-7delinsA variant is causative or at least contributory to disease but additional studies are necessary to determi ne its significance with certainty. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at