rs2229359

Variant names:

• chr10-8058684-C-T
• rs2229359
• NM_001002295.2:c.621C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001002295.2(GATA3):​c.621C>T​(p.Ala207Ala) 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:5
• Conservation: PhyloP100: -0.582
• Publications: 14 publications found

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 Gene-Disease associations (from GenCC):

• hypoparathyroidism-deafness-renal disease syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 256854.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 rank	MANE	Protein	UniProt
GATA3	NM_001002295.2	c.621C>T	p.Ala207Ala	synonymous_variant	Exon 3 of 6	ENST00000379328.9	NP_001002295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATA3	ENST00000379328.9	c.621C>T	p.Ala207Ala	synonymous_variant	Exon 3 of 6	1	NM_001002295.2	ENSP00000368632.3
GATA3	ENST00000346208.4	c.621C>T	p.Ala207Ala	synonymous_variant	Exon 3 of 6	1		ENSP00000341619.3
GATA3	ENST00000461472.1	c.285C>T	p.Ala95Ala	synonymous_variant	Exon 1 of 3	3		ENSP00000515407.1
GATA3	ENST00000481743.2	c.*190C>T		downstream_gene_variant		2		ENSP00000493486.1

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

GnomAD2 exomes AF: 0.0477 AC: 11938 AN: 250100 AF XY: 0.0475

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 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

African (AFR) AF: 0.0100 AC: 335 AN: 33478

American (AMR) AF: 0.0228 AC: 1021 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0326 AC: 851 AN: 26130

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39696

South Asian (SAS) AF: 0.00806 AC: 695 AN: 86258

European-Finnish (FIN) AF: 0.0963 AC: 5057 AN: 52520

Middle Eastern (MID) AF: 0.0212 AC: 122 AN: 5768

European-Non Finnish (NFE) AF: 0.0738 AC: 82033 AN: 1111964

Other (OTH) AF: 0.0516 AC: 3113 AN: 60382

GnomAD4 genome AF: 0.0493 AC: 7500 AN: 152262 Hom.: 262 Cov.: 33 AF XY: 0.0500 AC XY: 3722 AN XY: 74446

African (AFR) AF: 0.0132 AC: 550 AN: 41572

American (AMR) AF: 0.0304 AC: 466 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0308 AC: 107 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.00724 AC: 35 AN: 4832

European-Finnish (FIN) AF: 0.111 AC: 1178 AN: 10618

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0736 AC: 5004 AN: 67992

Other (OTH) AF: 0.0449 AC: 95 AN: 2114

Alfa AF: 0.0602 Hom.: 519

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:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

May 09, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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.

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

Hypoparathyroidism, deafness, renal disease syndrome Benign:1

Jan 13, 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	-0.63
CADD	Benign	9.4
DANN	Benign	0.84
PhyloP100		-0.58
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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