rs1058240

Variant names:

• chr10-8074635-G-A
• rs1058240
• NM_001002295.2:c.*612G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-8074635-G-A
• chr10-8074635-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001002295.2(GATA3):​c.*612G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.824 in 233,718 control chromosomes in the GnomAD database, including 79,772 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.81 (50536 hom., cov: 34)
  • Exomes 𝑓: 0.84 (29236 hom.)
• Consequence: GATA3 NM_001002295.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.463
• Publications: 24 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA3	NM_001002295.2	c.*612G>A		3_prime_UTR_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.*612G>A		3_prime_UTR_variant	Exon 6 of 6	1	NM_001002295.2	ENSP00000368632.3
GATA3	ENST00000346208.4	c.*612G>A		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000341619.3

Frequencies

GnomAD3 genomes AF: 0.814 AC: 123734 AN: 152098 Hom.: 50495 Cov.: 34

Gnomad AFR AF: 0.763

Gnomad AMI AF: 0.896

Gnomad AMR AF: 0.861

Gnomad ASJ AF: 0.905

Gnomad EAS AF: 0.977

Gnomad SAS AF: 0.931

Gnomad FIN AF: 0.832

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.803

Gnomad OTH AF: 0.829

GnomAD4 exome AF: 0.844 AC: 68779 AN: 81502 Hom.: 29236 Cov.: 0 AF XY: 0.844 AC XY: 31688 AN XY: 37526

African (AFR) AF: 0.762 AC: 2970 AN: 3900

American (AMR) AF: 0.886 AC: 2215 AN: 2500

Ashkenazi Jewish (ASJ) AF: 0.898 AC: 4602 AN: 5124

East Asian (EAS) AF: 0.983 AC: 11212 AN: 11402

South Asian (SAS) AF: 0.919 AC: 645 AN: 702

European-Finnish (FIN) AF: 0.817 AC: 397 AN: 486

Middle Eastern (MID) AF: 0.879 AC: 436 AN: 496

European-Non Finnish (NFE) AF: 0.812 AC: 40663 AN: 50108

Other (OTH) AF: 0.831 AC: 5639 AN: 6784

GnomAD4 genome AF: 0.814 AC: 123832 AN: 152216 Hom.: 50536 Cov.: 34 AF XY: 0.818 AC XY: 60855 AN XY: 74434

African (AFR) AF: 0.763 AC: 31673 AN: 41514

American (AMR) AF: 0.862 AC: 13187 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.905 AC: 3143 AN: 3472

East Asian (EAS) AF: 0.977 AC: 5067 AN: 5188

South Asian (SAS) AF: 0.931 AC: 4497 AN: 4828

European-Finnish (FIN) AF: 0.832 AC: 8807 AN: 10586

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.803 AC: 54623 AN: 68004

Other (OTH) AF: 0.831 AC: 1756 AN: 2114

Alfa AF: 0.814 Hom.: 105614

Bravo AF: 0.817

Asia WGS AF: 0.935 AC: 3250 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

-

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	-0.95
CADD	Benign	0.013
DANN	Benign	0.53
PhyloP100		-0.46
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: rs1058240; hg19: chr10-8116598;