rs778560008
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_021167.5(GATAD1):āc.766A>Gā(p.Thr256Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000093 in 1,612,288 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Genomes: š 0.000053 ( 0 hom., cov: 32)
Exomes š: 0.0000048 ( 0 hom. )
Consequence
GATAD1
NM_021167.5 missense
NM_021167.5 missense
Scores
1
4
14
Clinical Significance
Conservation
PhyloP100: 5.60
Genes affected
GATAD1 (HGNC:29941): (GATA zinc finger domain containing 1) The protein encoded by this gene contains a zinc finger at the N-terminus, and is thought to bind to a histone modification site that regulates gene expression. Mutations in this gene have been associated with autosomal recessive dilated cardiomyopathy. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2012]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.14510348).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GATAD1 | NM_021167.5 | c.766A>G | p.Thr256Ala | missense_variant | 5/5 | ENST00000287957.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GATAD1 | ENST00000287957.5 | c.766A>G | p.Thr256Ala | missense_variant | 5/5 | 1 | NM_021167.5 | P1 | |
GATAD1 | ENST00000493878.1 | n.1374A>G | non_coding_transcript_exon_variant | 3/3 | 1 | ||||
GATAD1 | ENST00000465247.1 | n.778A>G | non_coding_transcript_exon_variant | 2/2 | 2 | ||||
GATAD1 | ENST00000645746.1 | c.*357A>G | 3_prime_UTR_variant, NMD_transcript_variant | 6/6 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152106Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000240 AC: 6AN: 249720Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134914
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GnomAD4 exome AF: 0.00000479 AC: 7AN: 1460182Hom.: 0 Cov.: 29 AF XY: 0.00000413 AC XY: 3AN XY: 726348
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GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152106Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74296
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Dilated cardiomyopathy 2B Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 20, 2018 | This sequence change replaces threonine with alanine at codon 256 of the GATAD1 protein (p.Thr256Ala). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and alanine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with GATAD1-related disease. This variant is present in population databases (rs778560008, ExAC 0.01%). - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Nov 04, 2021 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 10, 2021 | The p.T256A variant (also known as c.766A>G), located in coding exon 5 of the GATAD1 gene, results from an A to G substitution at nucleotide position 766. The threonine at codon 256 is replaced by alanine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
B
Vest4
MVP
MPC
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