chrX-48792103-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_002049.4(GATA1):āc.480T>Gā(p.Asn160Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,977 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N160S) has been classified as Benign.
Frequency
Consequence
NM_002049.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GATA1 | NM_002049.4 | c.480T>G | p.Asn160Lys | missense_variant | 3/6 | ENST00000376670.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GATA1 | ENST00000376670.9 | c.480T>G | p.Asn160Lys | missense_variant | 3/6 | 1 | NM_002049.4 | P4 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD4 exome AF: 9.11e-7 AC: 1AN: 1097977Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 363351
GnomAD4 genome Cov.: 23
ClinVar
Submissions by phenotype
Diamond-Blackfan anemia;C1845837:GATA binding protein 1 related thrombocytopenia with dyserythropoiesis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 08, 2017 | This variant has not been reported in the literature in individuals with GATA1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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. This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with lysine at codon 160 of the GATA1 protein (p.Asn160Lys). The asparagine residue is weakly conserved and there is a moderate physicochemical difference between asparagine and lysine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at