rs2229359

Positions:

chr10-8058684-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001002295.2(GATA3):c.621C>T(p.Ala207=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0624 in 1,613,182 control chromosomes in the GnomAD database, including 3,788 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.049 ( 262 hom., cov: 33)

Exomes 𝑓: 0.064 ( 3526 hom. )

Consequence

GATA3
NM_001002295.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.582

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=-0.63).

BP6

Variant 10-8058684-C-T is Benign according to our data. Variant chr10-8058684-C-T is described in ClinVar as [Benign]. Clinvar id is 256854.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-8058684-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.582 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATA3	NM_001002295.2 linkuse as main transcript	c.621C>T	p.Ala207=	synonymous_variant	3/6	ENST00000379328.9	NP_001002295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATA3	ENST00000379328.9 linkuse as main transcript	c.621C>T	p.Ala207=	synonymous_variant	3/6	1	NM_001002295.2	ENSP00000368632	A1	P23771-2
GATA3	ENST00000346208.4 linkuse as main transcript	c.621C>T	p.Ala207=	synonymous_variant	3/6	1		ENSP00000341619	P4	P23771-1
GATA3	ENST00000461472.1 linkuse as main transcript	c.288C>T	p.Ala96=	synonymous_variant	1/3	3		ENSP00000515407

Frequencies

GnomAD3 genomes

AF:

0.0493

AC:

7501

AN:

152144

Hom.:

262

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0133

Gnomad AMI

AF:

0.0647

Gnomad AMR

AF:

0.0306

Gnomad ASJ

AF:

0.0308

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00724

Gnomad FIN

AF:

0.111

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0736

Gnomad OTH

AF:

0.0454

GnomAD3 exomes

AF:

0.0477

AC:

11938

AN:

250100

Hom.:

387

AF XY:

0.0475

AC XY:

6428

AN XY:

135444

show subpopulations

Gnomad AFR exome

AF:

0.0113

Gnomad AMR exome

AF:

0.0215

Gnomad ASJ exome

AF:

0.0308

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00781

Gnomad FIN exome

AF:

0.0988

Gnomad NFE exome

AF:

0.0713

Gnomad OTH exome

AF:

0.0512

GnomAD4 exome

AF:

0.0638

AC:

93232

AN:

1460920

Hom.:

3526

Cov.:

AF XY:

0.0619

AC XY:

45007

AN XY:

726860

show subpopulations

Gnomad4 AFR exome

AF:

0.0100

Gnomad4 AMR exome

AF:

0.0228

Gnomad4 ASJ exome

AF:

0.0326

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00806

Gnomad4 FIN exome

AF:

0.0963

Gnomad4 NFE exome

AF:

0.0738

Gnomad4 OTH exome

AF:

0.0516

GnomAD4 genome

AF:

0.0493

AC:

7500

AN:

152262

Hom.:

262

Cov.:

AF XY:

0.0500

AC XY:

3722

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0132

Gnomad4 AMR

AF:

0.0304

Gnomad4 ASJ

AF:

0.0308

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00724

Gnomad4 FIN

AF:

0.111

Gnomad4 NFE

AF:

0.0736

Gnomad4 OTH

AF:

0.0449

Alfa

AF:

0.0621

Hom.:

438

Bravo

AF:

0.0414

Asia WGS

AF:

0.00722

AC:

AN:

3478

EpiCase

AF:

0.0674

EpiControl

AF:

0.0644

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 09, 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. -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	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

-0.63

CADD

Benign

9.4

DANN

Benign

0.84

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