chr10-8073738-G-C
Position:
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PVS1PM2PP3_StrongPP5_Moderate
The NM_001002295.2(GATA3):c.1051-1G>C variant causes a splice acceptor change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
GATA3
NM_001002295.2 splice_acceptor
NM_001002295.2 splice_acceptor
Scores
3
3
1
Splicing: ADA: 1.000
2
Clinical Significance
Conservation
PhyloP100: 10.0
Genes affected
GATA3 (HGNC:4172): (GATA binding protein 3) This gene encodes a protein which belongs to the GATA family of transcription factors. The protein contains two GATA-type zinc fingers and is an important regulator of T-cell development and plays an important role in endothelial cell biology. Defects in this gene are the cause of hypoparathyroidism with sensorineural deafness and renal dysplasia. [provided by RefSeq, Nov 2009]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 16 ACMG points.
PVS1
Splicing variant, LoF is a know mechanism of disease, Cryptic splice site detected, with MaxEntScore 7.8, offset of 8, new splice context is: atctttgtttacattaacAGacc. Cryptic site results in frameshift change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
PM2
Very rare variant in population databases, with high coverage;
PP3
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
PP5
Variant 10-8073738-G-C is Pathogenic according to our data. Variant chr10-8073738-G-C is described in ClinVar as [Pathogenic]. Clinvar id is 430696.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GATA3 | NM_001002295.2 | c.1051-1G>C | splice_acceptor_variant | ENST00000379328.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GATA3 | ENST00000379328.9 | c.1051-1G>C | splice_acceptor_variant | 1 | NM_001002295.2 | A1 | |||
GATA3 | ENST00000346208.4 | c.1048-1G>C | splice_acceptor_variant | 1 | P4 | ||||
GATA3 | ENST00000461472.1 | c.570-1G>C | splice_acceptor_variant | 3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 35
GnomAD4 exome
Cov.:
35
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Stage 5 chronic kidney disease Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Bioinformatics dept., Datar Cancer Genetics Limited, India | Nov 02, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
D;D
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 9
DS_AL_spliceai
Position offset: 1
Find out detailed SpliceAI scores and Pangolin per-transcript scores at