chrX-48791126-TG-T
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_002049.4(GATA1):c.21del(p.Ser8ProfsTer129) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 22)
Consequence
GATA1
NM_002049.4 frameshift
NM_002049.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.164
Genes affected
GATA1 (HGNC:4170): (GATA binding protein 1) This gene encodes a protein which belongs to the GATA family of transcription factors. The protein plays an important role in erythroid development by regulating the switch of fetal hemoglobin to adult hemoglobin. Mutations in this gene have been associated with X-linked dyserythropoietic anemia and thrombocytopenia. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 45 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant X-48791126-TG-T is Pathogenic according to our data. Variant chrX-48791126-TG-T is described in ClinVar as [Pathogenic]. Clinvar id is 465133.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GATA1 | NM_002049.4 | c.21del | p.Ser8ProfsTer129 | frameshift_variant | 2/6 | ENST00000376670.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GATA1 | ENST00000376670.9 | c.21del | p.Ser8ProfsTer129 | frameshift_variant | 2/6 | 1 | NM_002049.4 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD3 genomes
?
Cov.:
22
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 22
GnomAD4 genome
?
Cov.:
22
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Diamond-Blackfan anemia;C1845837:GATA binding protein 1 related thrombocytopenia with dyserythropoiesis Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Sep 03, 2017 | For these reasons, this variant has been classified as Pathogenic. This variant is expected to result in a truncated GATA1 protein that lacks the N-terminal zinc-finger (residues 198-233) and C-terminal zinc-finger (residues 254-286). These domains mediate not only DNA binding, but also the majority of protein-protein interactions required for the proper transcriptional regulatory function of the GATA1 protein (PMID: 11566888, 16095949, 8628290, 15920471, 24255919). Several missense variants that result in disrupted function of the GATA1 protein have been reported in individuals affected with GATA1-related disease, indicating that loss-of-function variants in GATA1 are pathogenic (PMID: 23704091). This variant has not been reported in the literature in individuals with GATA1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ser8Profs*129) in the GATA1 gene. It is expected to result in an absent or disrupted protein product. - |
Computational scores
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Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
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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