rs540654499
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_021167.5(GATAD1):c.512G>A(p.Arg171Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,613,328 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.000098 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000082 ( 0 hom. )
Consequence
GATAD1
NM_021167.5 missense
NM_021167.5 missense
Scores
5
9
5
Clinical Significance
Conservation
PhyloP100: 9.79
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 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GATAD1 | NM_021167.5 | c.512G>A | p.Arg171Lys | missense_variant | 4/5 | ENST00000287957.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GATAD1 | ENST00000287957.5 | c.512G>A | p.Arg171Lys | missense_variant | 4/5 | 1 | NM_021167.5 | P1 | |
GATAD1 | ENST00000493878.1 | n.1120G>A | non_coding_transcript_exon_variant | 2/3 | 1 | ||||
GATAD1 | ENST00000465247.1 | n.524G>A | non_coding_transcript_exon_variant | 1/2 | 2 | ||||
GATAD1 | ENST00000645746.1 | c.*103G>A | 3_prime_UTR_variant, NMD_transcript_variant | 5/6 |
Frequencies
GnomAD3 genomes ? AF: 0.0000985 AC: 15AN: 152220Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251390Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135866
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GnomAD4 exome AF: 0.00000821 AC: 12AN: 1460988Hom.: 0 Cov.: 29 AF XY: 0.00000963 AC XY: 7AN XY: 726886
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GnomAD4 genome ? AF: 0.0000985 AC: 15AN: 152340Hom.: 0 Cov.: 32 AF XY: 0.0000940 AC XY: 7AN XY: 74490
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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 | Fulgent Genetics, Fulgent Genetics | Nov 04, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 09, 2023 | This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 171 of the GATAD1 protein (p.Arg171Lys). This variant is present in population databases (rs540654499, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with GATAD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 581797). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt GATAD1 protein function. 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. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 14, 2023 | The p.R171K variant (also known as c.512G>A), located in coding exon 4 of the GATAD1 gene, results from a G to A substitution at nucleotide position 512. The arginine at codon 171 is replaced by lysine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious 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
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D
REVEL
Pathogenic
Sift
Benign
D
Sift4G
Benign
T
Polyphen
B
Vest4
MVP
MPC
ClinPred
D
GERP RS
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