10-8074116-C-T

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.*93C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0239 in 1,408,806 control chromosomes in the GnomAD database, including 2,126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (234 hom., cov: 32)
  • Exomes 𝑓: 0.024 (1892 hom.)
• Consequence: GATA3 NM_001002295.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.849

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=-0.88).
• BP6: Variant 10-8074116-C-T is Benign according to our data. Variant chr10-8074116-C-T is described in ClinVar as [Benign]. Clinvar id is 301131.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATA3	NM_001002295.2	c.*93C>T		3_prime_UTR_variant	6/6	ENST00000379328.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATA3	ENST00000379328.9	c.*93C>T		3_prime_UTR_variant	6/6	1	NM_001002295.2	A1
GATA3	ENST00000346208.4	c.*93C>T		3_prime_UTR_variant	6/6	1		P4

Frequencies

GnomAD3 genomes AF: 0.0262 AC: 3988 AN: 152122 Hom.: 235 Cov.: 32

Gnomad AFR AF: 0.00480

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0123

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.0702

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0112

Gnomad OTH AF: 0.0191

GnomAD4 exome AF: 0.0236 AC: 29686 AN: 1256566 Hom.: 1892 Cov.: 18 AF XY: 0.0246 AC XY: 15365 AN XY: 625492

Gnomad4 AFR exome AF: 0.00515

Gnomad4 AMR exome AF: 0.0232

Gnomad4 ASJ exome AF: 0.00759

Gnomad4 EAS exome AF: 0.275

Gnomad4 SAS exome AF: 0.0545

Gnomad4 FIN exome AF: 0.0958

Gnomad4 NFE exome AF: 0.00888

Gnomad4 OTH exome AF: 0.0288

GnomAD4 genome AF: 0.0262 AC: 3989 AN: 152240 Hom.: 234 Cov.: 32 AF XY: 0.0322 AC XY: 2396 AN XY: 74424

Gnomad4 AFR AF: 0.00476

Gnomad4 AMR AF: 0.0123

Gnomad4 ASJ AF: 0.0107

Gnomad4 EAS AF: 0.261

Gnomad4 SAS AF: 0.0715

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.0112

Gnomad4 OTH AF: 0.0185

Alfa AF: 0.0109 Hom.: 45

Bravo AF: 0.0204

Asia WGS AF: 0.120 AC: 414 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

clinical testing

GeneDx

Jul 05, 2018

- -

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	-0.88
Cadd	Benign	0.19
Dann	Benign	0.58

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: rs2229360; hg19: chr10-8116079; COSMIC: COSV60523713; COSMIC: COSV60523713;