10-8058636-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001002295.2(GATA3):c.573C>T(p.Pro191Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00579 in 1,612,860 control chromosomes in the GnomAD database, including 115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0049 ( 12 hom., cov: 33)

Exomes 𝑓: 0.0059 ( 103 hom. )

Consequence

GATA3
NM_001002295.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.19

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 Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 10-8058636-C-T is Benign according to our data. Variant chr10-8058636-C-T is described in ClinVar as [Benign]. Clinvar id is 301122.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.19 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00493 (751/152244) while in subpopulation SAS AF= 0.0263 (127/4824). AF 95% confidence interval is 0.0226. There are 12 homozygotes in gnomad4. There are 404 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 751 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA3	NM_001002295.2 link	c.573C>T	p.Pro191Pro	synonymous_variant	Exon 3 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.573C>T	p.Pro191Pro	synonymous_variant	Exon 3 of 6	1	NM_001002295.2	ENSP00000368632.3	P23771-2
GATA3	ENST00000346208.4 link	c.573C>T	p.Pro191Pro	synonymous_variant	Exon 3 of 6	1		ENSP00000341619.3	P23771-1
GATA3	ENST00000461472.1 link	c.237C>T	p.Pro79Pro	synonymous_variant	Exon 1 of 3	3		ENSP00000515407.1	A0A994J6H6
GATA3	ENST00000481743.2 link	c.*142C>T		downstream_gene_variant		2		ENSP00000493486.1	A0A2R8Y2A9

Frequencies

GnomAD3 genomes

AF:

0.00496

AC:

754

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000628

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00523

Gnomad ASJ

AF:

0.0285

Gnomad EAS

AF:

0.000580

Gnomad SAS

AF:

0.0259

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.00534

Gnomad OTH

AF:

0.0124

GnomAD3 exomes

AF:

0.00861

AC:

2150

AN:

249642

Hom.:

AF XY:

0.0102

AC XY:

1384

AN XY:

135266

show subpopulations

Gnomad AFR exome

AF:

0.000804

Gnomad AMR exome

AF:

0.00379

Gnomad ASJ exome

AF:

0.0335

Gnomad EAS exome

AF:

0.000164

Gnomad SAS exome

AF:

0.0271

Gnomad FIN exome

AF:

0.00155

Gnomad NFE exome

AF:

0.00649

Gnomad OTH exome

AF:

0.0118

GnomAD4 exome

AF:

0.00588

AC:

8591

AN:

1460616

Hom.:

103

Cov.:

AF XY:

0.00687

AC XY:

4996

AN XY:

726702

show subpopulations

Gnomad4 AFR exome

AF:

0.000418

Gnomad4 AMR exome

AF:

0.00445

Gnomad4 ASJ exome

AF:

0.0325

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0294

Gnomad4 FIN exome

AF:

0.00197

Gnomad4 NFE exome

AF:

0.00372

Gnomad4 OTH exome

AF:

0.00898

GnomAD4 genome

AF:

0.00493

AC:

751

AN:

152244

Hom.:

Cov.:

AF XY:

0.00543

AC XY:

404

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.000626

Gnomad4 AMR

AF:

0.00523

Gnomad4 ASJ

AF:

0.0285

Gnomad4 EAS

AF:

0.000582

Gnomad4 SAS

AF:

0.0263

Gnomad4 FIN

AF:

0.00160

Gnomad4 NFE

AF:

0.00532

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.00740

Hom.:

Bravo

AF:

0.00468

Asia WGS

AF:

0.00924

AC:

AN:

3478

EpiCase

AF:

0.00900

EpiControl

AF:

0.00990

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Feb 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 12, 2019

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 17, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Mar 21, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

p.Pro191Pro in exon 3 of GATA3: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 2.70% (445/16486) of South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac. broadinstitute.org; dbSNP rs35508267). -

Hypoparathyroidism, deafness, renal disease syndrome

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

6.4

DANN

Benign

0.93

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