rs2229359

chr10-8058684-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.582

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]

ACMG classification

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	UniProt
GATA3	NM_001002295.2	c.621C>T	p.Ala207=	synonymous_variant	3/6	ENST00000379328.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATA3	ENST00000379328.9	c.621C>T	p.Ala207=	synonymous_variant	3/6	1	NM_001002295.2	A1
GATA3	ENST00000346208.4	c.621C>T	p.Ala207=	synonymous_variant	3/6	1		P4
GATA3	ENST00000461472.1	c.288C>T	p.Ala96=	synonymous_variant	1/3	3

Frequencies

GnomAD3 genomes AF: 0.0493 AC: 7501 AN: 152144 Hom.: 262 Cov.: 33

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

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.: 35 AF XY: 0.0619 AC XY: 45007 AN XY: 726860

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.: 33 AF XY: 0.0500 AC XY: 3722 AN XY: 74446

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: 27 AN: 3478

EpiCase AF: 0.0674

EpiControl AF: 0.0644

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

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: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	-0.63
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

Other links and lift over

dbSNP: rs2229359; hg19: chr10-8100647; COSMIC: COSV60519981; COSMIC: COSV60519981;