rs11567941

Variant names:

• chr10-8073945-G-A
• rs11567941
• NM_001002295.2:c.1257G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-8073945-G-A
• chr10-8073945-G-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001002295.2(GATA3):​c.1257G>A​(p.Thr419Thr) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.01
• Publications: 7 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=-0.65).
• BP6: Variant 10-8073945-G-A is Benign according to our data. Variant chr10-8073945-G-A is described in ClinVar as Benign. ClinVar VariationId is 256852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 4692 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA3	NM_001002295.2	c.1257G>A	p.Thr419Thr	synonymous_variant	Exon 6 of 6	ENST00000379328.9	NP_001002295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATA3	ENST00000379328.9	c.1257G>A	p.Thr419Thr	synonymous_variant	Exon 6 of 6	1	NM_001002295.2	ENSP00000368632.3
GATA3	ENST00000346208.4	c.1254G>A	p.Thr418Thr	synonymous_variant	Exon 6 of 6	1		ENSP00000341619.3
GATA3	ENST00000461472.1	c.*202G>A		3_prime_UTR_variant	Exon 3 of 3	3		ENSP00000515407.1

Frequencies

GnomAD3 genomes AF: 0.0309 AC: 4696 AN: 151980 Hom.: 106 Cov.: 32

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

GnomAD2 exomes AF: 0.0302 AC: 7590 AN: 251276 AF XY: 0.0301

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 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.: 35 AF XY: 0.0411 AC XY: 29877 AN XY: 727230

African (AFR) AF: 0.00711 AC: 238 AN: 33480

American (AMR) AF: 0.0276 AC: 1234 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0336 AC: 878 AN: 26136

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.00634 AC: 547 AN: 86258

European-Finnish (FIN) AF: 0.0197 AC: 1051 AN: 53402

Middle Eastern (MID) AF: 0.0300 AC: 173 AN: 5768

European-Non Finnish (NFE) AF: 0.0497 AC: 55246 AN: 1111990

Other (OTH) AF: 0.0406 AC: 2455 AN: 60396

GnomAD4 genome AF: 0.0308 AC: 4692 AN: 152098 Hom.: 106 Cov.: 32 AF XY: 0.0295 AC XY: 2196 AN XY: 74334

African (AFR) AF: 0.00887 AC: 368 AN: 41496

American (AMR) AF: 0.0463 AC: 707 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0314 AC: 109 AN: 3468

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5170

South Asian (SAS) AF: 0.00603 AC: 29 AN: 4812

European-Finnish (FIN) AF: 0.0153 AC: 162 AN: 10578

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0472 AC: 3211 AN: 67990

Other (OTH) AF: 0.0460 AC: 97 AN: 2108

Alfa AF: 0.0402 Hom.: 68

Bravo AF: 0.0338

Asia WGS AF: 0.00520 AC: 18 AN: 3478

EpiCase AF: 0.0464

EpiControl AF: 0.0478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Aug 16, 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. -

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PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

Jan 29, 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	-0.65
CADD	Benign	1.6
DANN	Benign	0.85
PhyloP100		-2.0
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: rs11567941; hg19: chr10-8115908;