rs11567941

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001002295.2(GATA3):c.1257G>A(p.Thr419=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0412 in 1,613,952 control chromosomes in the GnomAD database, including 1,685 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 106 hom., cov: 32)

Exomes 𝑓: 0.042 ( 1579 hom. )

Consequence

GATA3
NM_001002295.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.01

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 10-8073945-G-A is Benign according to our data. Variant chr10-8073945-G-A is described in ClinVar as [Benign]. Clinvar id is 256852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-8073945-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.01 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0308 (4692/152098) while in subpopulation NFE AF= 0.0472 (3211/67990). AF 95% confidence interval is 0.0459. There are 106 homozygotes in gnomad4. There are 2196 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 4692 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATA3	NM_001002295.2 linkuse as main transcript	c.1257G>A	p.Thr419=	synonymous_variant	6/6	ENST00000379328.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATA3	ENST00000379328.9 linkuse as main transcript	c.1257G>A	p.Thr419=	synonymous_variant	6/6	1	NM_001002295.2	A1	P23771-2
GATA3	ENST00000346208.4 linkuse as main transcript	c.1254G>A	p.Thr418=	synonymous_variant	6/6	1		P4	P23771-1
GATA3	ENST00000461472.1 linkuse as main transcript	c.*202G>A		3_prime_UTR_variant	3/3	3

Frequencies

GnomAD3 genomes

AF:

0.0309

AC:

4696

AN:

151980

Hom.:

106

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00894

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0464

Gnomad ASJ

AF:

0.0314

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00602

Gnomad FIN

AF:

0.0153

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0472

Gnomad OTH

AF:

0.0465

GnomAD3 exomes

AF:

0.0302

AC:

7590

AN:

251276

Hom.:

160

AF XY:

0.0301

AC XY:

4089

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.00751

Gnomad AMR exome

AF:

0.0267

Gnomad ASJ exome

AF:

0.0368

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00621

Gnomad FIN exome

AF:

0.0172

Gnomad NFE exome

AF:

0.0470

Gnomad OTH exome

AF:

0.0432

GnomAD4 exome

AF:

0.0423

AC:

61825

AN:

1461854

Hom.:

1579

Cov.:

AF XY:

0.0411

AC XY:

29877

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.00711

Gnomad4 AMR exome

AF:

0.0276

Gnomad4 ASJ exome

AF:

0.0336

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00634

Gnomad4 FIN exome

AF:

0.0197

Gnomad4 NFE exome

AF:

0.0497

Gnomad4 OTH exome

AF:

0.0406

GnomAD4 genome

AF:

0.0308

AC:

4692

AN:

152098

Hom.:

106

Cov.:

AF XY:

0.0295

AC XY:

2196

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.00887

Gnomad4 AMR

AF:

0.0463

Gnomad4 ASJ

AF:

0.0314

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00603

Gnomad4 FIN

AF:

0.0153

Gnomad4 NFE

AF:

0.0472

Gnomad4 OTH

AF:

0.0460

Alfa

AF:

0.0402

Hom.:

Bravo

AF:

0.0338

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.0464

EpiControl

AF:

0.0478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 16, 2017	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Hypoparathyroidism, deafness, renal disease syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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

-0.65

CADD

Benign

1.6

DANN

Benign

0.85

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