rs782653725
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM1BP6BS2
The NM_000116.5(TAFAZZIN):c.758G>A(p.Arg253Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000198 in 1,209,097 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000027 ( 0 hom., 2 hem., cov: 23)
Exomes 𝑓: 0.000019 ( 0 hom. 4 hem. )
Consequence
TAFAZZIN
NM_000116.5 missense
NM_000116.5 missense
Scores
3
6
8
Clinical Significance
Conservation
PhyloP100: 3.70
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 Likely_benign. Variant got -3 ACMG points.
PM1
In a topological_domain Mitochondrial intermembrane (size 226) in uniprot entity TAZ_HUMAN there are 6 pathogenic changes around while only 0 benign (100%) in NM_000116.5
BP6
Variant X-154420716-G-A is Benign according to our data. Variant chrX-154420716-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 234467.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=2}.
BS2
High Hemizygotes in GnomAd4 at 2 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TAFAZZIN | NM_000116.5 | c.758G>A | p.Arg253Gln | missense_variant | 10/11 | ENST00000601016.6 | NP_000107.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TAFAZZIN | ENST00000601016.6 | c.758G>A | p.Arg253Gln | missense_variant | 10/11 | 1 | NM_000116.5 | ENSP00000469981 |
Frequencies
GnomAD3 genomes AF: 0.0000271 AC: 3AN: 110901Hom.: 0 Cov.: 23 AF XY: 0.0000604 AC XY: 2AN XY: 33099
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GnomAD3 exomes AF: 0.0000273 AC: 5AN: 183443Hom.: 0 AF XY: 0.0000147 AC XY: 1AN XY: 67893
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GnomAD4 exome AF: 0.0000191 AC: 21AN: 1098196Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 4AN XY: 363556
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GnomAD4 genome AF: 0.0000271 AC: 3AN: 110901Hom.: 0 Cov.: 23 AF XY: 0.0000604 AC XY: 2AN XY: 33099
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Aug 16, 2016 | - - |
3-Methylglutaconic aciduria type 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 20, 2022 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 253 of the TAZ protein (p.Arg253Gln). This variant is present in population databases (rs782653725, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with TAZ-related conditions. ClinVar contains an entry for this variant (Variation ID: 234467). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 22, 2019 | This variant is associated with the following publications: (PMID: 31094706) - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Pathogenic
DEOGEN2
Benign
.;.;.;T;.
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
.;.;.;M;.
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
.;.;.;.;N
REVEL
Uncertain
Sift
Benign
.;.;.;.;T
Sift4G
Benign
T;T;T;T;D
Polyphen
P;P;D;D;.
Vest4
MutPred
0.50
.;.;.;Loss of MoRF binding (P = 0.0814);.;
MVP
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at