rs1058240

Positions:

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

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_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. Variant has been reported in ClinVar as Benign (★★).

• 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

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 10-8074635-G-A is Benign according to our data. Variant chr10-8074635-G-A is described in ClinVar as [Benign]. Clinvar id is 301140.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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/exons	MANE	Protein	UniProt
GATA3	NM_001002295.2	c.*612G>A		3_prime_UTR_variant	6/6	ENST00000379328.9	NP_001002295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATA3	ENST00000379328.9	c.*612G>A		3_prime_UTR_variant	6/6	1	NM_001002295.2	ENSP00000368632	A1
GATA3	ENST00000346208.4	c.*612G>A		3_prime_UTR_variant	6/6	1		ENSP00000341619	P4

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

Gnomad4 AFR exome AF: 0.762

Gnomad4 AMR exome AF: 0.886

Gnomad4 ASJ exome AF: 0.898

Gnomad4 EAS exome AF: 0.983

Gnomad4 SAS exome AF: 0.919

Gnomad4 FIN exome AF: 0.817

Gnomad4 NFE exome AF: 0.812

Gnomad4 OTH exome AF: 0.831

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

Gnomad4 AFR AF: 0.763

Gnomad4 AMR AF: 0.862

Gnomad4 ASJ AF: 0.905

Gnomad4 EAS AF: 0.977

Gnomad4 SAS AF: 0.931

Gnomad4 FIN AF: 0.832

Gnomad4 NFE AF: 0.803

Gnomad4 OTH AF: 0.831

Alfa AF: 0.816 Hom.: 70993

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

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

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	-0.95
CADD	Benign	0.013
DANN	Benign	0.53

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: rs1058240; hg19: chr10-8116598;