chrX-48791103-AGGCTCCATGGAGTTCCCTGGCCTGG-A
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_002049.4(GATA1):c.-4_21del variant causes a start lost, 5 prime UTR change. 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 start_lost, 5_prime_UTR
NM_002049.4 start_lost, 5_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.28
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
?
Start lost variant, no new inframe start found.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant X-48791103-AGGCTCCATGGAGTTCCCTGGCCTGG-A is Pathogenic according to our data. Variant chrX-48791103-AGGCTCCATGGAGTTCCCTGGCCTGG-A is described in ClinVar as [Pathogenic]. Clinvar id is 2952845.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.-4_21del | start_lost, 5_prime_UTR_variant | 2/6 | ENST00000376670.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GATA1 | ENST00000376670.9 | c.-4_21del | start_lost, 5_prime_UTR_variant | 2/6 | 1 | NM_002049.4 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD3 genomes
?
Cov.:
22
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
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 | Oct 14, 2023 | This sequence change affects the initiator methionine of the GATA1 mRNA. The next in-frame methionine is located at codon 1. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GATA1-related conditions. This variant disrupts a region of the GATA1 protein in which other variant(s) (p.Met1?) have been determined to be pathogenic (PMID: 24453067, 24952648, 29146883, 35328001; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.