X-154413249-G-C
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Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PP3_StrongPP5_Moderate
The NM_000116.5(TAFAZZIN):āc.281G>Cā(p.Arg94Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (ā ).
Frequency
Genomes: not found (cov: 24)
Exomes š: 0.0 ( 0 hom. 0 hem. )
Failed GnomAD Quality Control
Consequence
TAFAZZIN
NM_000116.5 missense
NM_000116.5 missense
Scores
12
4
1
Clinical Significance
Conservation
PhyloP100: 7.11
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.
PM1
In a chain Tafazzin (size 261) in uniprot entity TAZ_HUMAN there are 6 pathogenic changes around while only 0 benign (100%) in NM_000116.5
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.972
PP5
Variant X-154413249-G-C is Pathogenic according to our data. Variant chrX-154413249-G-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1202910.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TAFAZZIN | NM_000116.5 | c.281G>C | p.Arg94Pro | missense_variant | 3/11 | ENST00000601016.6 | NP_000107.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TAFAZZIN | ENST00000601016.6 | c.281G>C | p.Arg94Pro | missense_variant | 3/11 | 1 | NM_000116.5 | ENSP00000469981.1 |
Frequencies
GnomAD3 genomes Cov.: 24
GnomAD3 genomes
Cov.:
24
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1098052Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 363436
GnomAD4 exome
Data not reliable, filtered out with message: AC0
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0
AN:
1098052
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Cov.:
31
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0
AN XY:
363436
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 24
GnomAD4 genome
Cov.:
24
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Apr 11, 2019 | Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
.;.;.;.;.;D;.;D
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;D;D;.;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
.;M;M;.;M;M;.;.
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
.;.;D;.;.;.;D;D
REVEL
Pathogenic
Sift
Pathogenic
.;.;D;.;.;.;D;D
Sift4G
Pathogenic
D;D;D;D;D;D;D;D
Polyphen
1.0, 0.86, 0.033
.;D;D;.;P;B;.;.
Vest4
0.92, 0.91, 0.89, 0.90, 0.93
MutPred
0.87
.;Loss of MoRF binding (P = 0.002);Loss of MoRF binding (P = 0.002);.;Loss of MoRF binding (P = 0.002);Loss of MoRF binding (P = 0.002);.;Loss of MoRF binding (P = 0.002);
MVP
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.