rs1418790540
Positions:
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM1BP4BS2
The NM_002049.4(GATA1):c.982G>A(p.Glu328Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000829 in 1,205,950 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.000035 ( 0 hom., 2 hem., cov: 23)
Exomes 𝑓: 0.0000055 ( 0 hom. 2 hem. )
Consequence
GATA1
NM_002049.4 missense
NM_002049.4 missense
Scores
1
7
9
Clinical Significance
Conservation
PhyloP100: 3.80
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 Likely_benign. Variant got -3 ACMG points.
PM1
?
In a region_of_interest Interaction with MED1 and CCAR1 (size 130) in uniprot entity GATA1_HUMAN there are 17 pathogenic changes around while only 2 benign (89%) in NM_002049.4
BP4
?
Computational evidence support a benign effect (MetaRNN=0.30478677).
BS2
?
High Hemizygotes in GnomAd4 at 2 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GATA1 | NM_002049.4 | c.982G>A | p.Glu328Lys | missense_variant | 6/6 | ENST00000376670.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GATA1 | ENST00000376670.9 | c.982G>A | p.Glu328Lys | missense_variant | 6/6 | 1 | NM_002049.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000354 AC: 4AN: 113050Hom.: 0 Cov.: 23 AF XY: 0.0000568 AC XY: 2AN XY: 35202
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GnomAD4 exome AF: 0.00000549 AC: 6AN: 1092900Hom.: 0 Cov.: 32 AF XY: 0.00000557 AC XY: 2AN XY: 358966
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GnomAD4 genome ? AF: 0.0000354 AC: 4AN: 113050Hom.: 0 Cov.: 23 AF XY: 0.0000568 AC XY: 2AN XY: 35202
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 17, 2016 | - - |
Diamond-Blackfan anemia;C1845837:GATA binding protein 1 related thrombocytopenia with dyserythropoiesis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2022 | This variant has not been reported in the literature in individuals affected with GATA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 328 of the GATA1 protein (p.Glu328Lys). ClinVar contains an entry for this variant (Variation ID: 435276). 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. 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 GATA1 protein function. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Benign
T
MetaSVM
Uncertain
D
MutationAssessor
Benign
N
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
D
Vest4
MutPred
Gain of ubiquitination at E328 (P = 0.0054);
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