X-154413249-G-C

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PP3_StrongPP5_Moderate

The NM_000116.5(TAFAZZIN):ā€‹c.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

Scores

12
4
1

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 7.11
Variant links:
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]

Genome browser will be placed here

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
TAFAZZINNM_000116.5 linkuse as main transcriptc.281G>C p.Arg94Pro missense_variant 3/11 ENST00000601016.6 NP_000107.1 Q16635-1A0A0S2Z4K0

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TAFAZZINENST00000601016.6 linkuse as main transcriptc.281G>C p.Arg94Pro missense_variant 3/111 NM_000116.5 ENSP00000469981.1 Q16635-1

Frequencies

GnomAD3 genomes
Cov.:
24
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1098052
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
363436
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
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 submitterclinical testingGeneDxApr 11, 2019Has 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.71
D
BayesDel_noAF
Pathogenic
0.78
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.83
.;.;.;.;.;D;.;D
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.97
.;D;D;.;D;D;D;D
M_CAP
Pathogenic
0.43
D
MetaRNN
Pathogenic
0.97
D;D;D;D;D;D;D;D
MetaSVM
Pathogenic
1.1
D
MutationAssessor
Pathogenic
3.3
.;M;M;.;M;M;.;.
PrimateAI
Uncertain
0.75
T
PROVEAN
Pathogenic
-6.5
.;.;D;.;.;.;D;D
REVEL
Pathogenic
0.93
Sift
Pathogenic
0.0
.;.;D;.;.;.;D;D
Sift4G
Pathogenic
0.0
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
1.0
ClinPred
1.0
D
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.98
gMVP
1.0

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-153641586; API