Variant 10-8055665-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001002295.2(GATA3):c.10A>G(p.Thr4Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,404,162 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

GATA3
NM_001002295.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.60

Variant links:

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]

GATA3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08573526).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATA3	NM_001002295.2 linkuse as main transcript	c.10A>G	p.Thr4Ala	missense_variant	2/6	ENST00000379328.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATA3	ENST00000379328.9 linkuse as main transcript	c.10A>G	p.Thr4Ala	missense_variant	2/6	1	NM_001002295.2	A1	P23771-2
GATA3	ENST00000346208.4 linkuse as main transcript	c.10A>G	p.Thr4Ala	missense_variant	2/6	1		P4	P23771-1
GATA3	ENST00000481743.2 linkuse as main transcript	c.10A>G	p.Thr4Ala	missense_variant	2/3	2
GATA3	ENST00000643001.1 linkuse as main transcript	c.10A>G	p.Thr4Ala	missense_variant	2/2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000129

AC:

AN:

155488

Hom.:

AF XY:

0.0000239

AC XY:

AN XY:

83702

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000237

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000214

AC:

AN:

1404162

Hom.:

Cov.:

AF XY:

0.00000288

AC XY:

AN XY:

693370

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000119

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Oct 07, 2022

In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

0.0084

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.35

.;.;.;.;T

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.83

T;T;.;T;T

M_CAP

Uncertain

0.20

MetaRNN

Benign

0.086

T;T;T;T;T

MetaSVM

Benign

-0.31

MutationAssessor

Benign

0.14

.;.;N;N;N

MutationTaster

Benign

0.83

N;N

PrimateAI

Uncertain

0.65

PROVEAN

Benign

0.35

.;.;N;.;N

REVEL

Benign

0.26

Sift

Benign

1.0

.;.;T;.;T

Sift4G

Benign

0.63

.;.;T;.;T

Polyphen

0.0, 0.0040

.;.;B;B;B

Vest4

0.039, 0.037

MutPred

0.15

Loss of glycosylation at T4 (P = 0.0374);Loss of glycosylation at T4 (P = 0.0374);Loss of glycosylation at T4 (P = 0.0374);Loss of glycosylation at T4 (P = 0.0374);Loss of glycosylation at T4 (P = 0.0374);

MVP

0.55

MPC

0.73

ClinPred

0.058

GERP RS

4.6

Varity_R

0.070

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over