Genetic Variant GATA3:p.Val18Ala (chr10-8055708-T-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001002295.2(GATA3):c.53T>C(p.Val18Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000256 in 1,564,628 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GATA3
NM_001002295.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.60

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA3	NM_001002295.2 link	c.53T>C	p.Val18Ala	missense_variant	Exon 2 of 6	ENST00000379328.9	NP_001002295.1	P23771-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GATA3	ENST00000379328.9 link	c.53T>C	p.Val18Ala	missense_variant	Exon 2 of 6	1	NM_001002295.2	ENSP00000368632.3	P23771-2
GATA3	ENST00000346208.4 link	c.53T>C	p.Val18Ala	missense_variant	Exon 2 of 6	1		ENSP00000341619.3	P23771-1
GATA3	ENST00000481743.2 link	c.53T>C	p.Val18Ala	missense_variant	Exon 2 of 3	2		ENSP00000493486.1	A0A2R8Y2A9
GATA3	ENST00000643001.1 link	c.53T>C	p.Val18Ala	missense_variant	Exon 2 of 2			ENSP00000494284.1	A0A2R8Y4T2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000589

AC:

AN:

169698

Hom.:

AF XY:

0.00

AC XY:

AN XY:

91250

show subpopulations

Gnomad AFR exome

AF:

0.000105

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

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:

0.00000142

AC:

AN:

1412474

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

698122

show subpopulations

Gnomad4 AFR exome

AF:

0.0000619

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

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

AF:

0.0000131

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.070

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.50

.;.;.;.;D

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

D;D;.;D;D

M_CAP

Pathogenic

0.59

MetaRNN

Uncertain

0.52

D;D;D;D;D

MetaSVM

Pathogenic

0.85

MutationAssessor

Benign

1.8

.;.;L;L;L

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.0

.;.;N;.;N

REVEL

Uncertain

0.57

Sift

Uncertain

0.0060

.;.;D;.;D

Sift4G

Benign

0.27

.;.;T;.;T

Polyphen

0.53, 0.68

.;.;P;P;P

Vest4

0.56, 0.57

MutPred

0.24

Loss of stability (P = 0.0332);Loss of stability (P = 0.0332);Loss of stability (P = 0.0332);Loss of stability (P = 0.0332);Loss of stability (P = 0.0332);

MVP

0.77

MPC

1.3

ClinPred

0.96

GERP RS

4.9

Varity_R

0.20

gMVP

0.51

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over