Genetic Variant GATA3:c.-264G>T (chr10-8055392-G-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001002295.2(GATA3):c.-264G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00203 in 559,390 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 7 hom., cov: 31)

Exomes 𝑓: 0.0024 ( 16 hom. )

Consequence

GATA3
NM_001002295.2 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.733

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 10-8055392-G-T is Benign according to our data. Variant chr10-8055392-G-T is described in ClinVar as [Benign]. Clinvar id is 301108.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00117 (178/152218) while in subpopulation EAS AF= 0.028 (145/5172). AF 95% confidence interval is 0.0243. There are 7 homozygotes in gnomad4. There are 111 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 178 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA3	NM_001002295.2 link	c.-264G>T		5_prime_UTR_variant	Exon 2 of 6	ENST00000379328.9	NP_001002295.1	P23771-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GATA3	ENST00000379328 link	c.-264G>T	5_prime_UTR_variant	Exon 2 of 6	1	NM_001002295.2	ENSP00000368632.3	P23771-2
GATA3	ENST00000346208 link	c.-264G>T	5_prime_UTR_variant	Exon 2 of 6	1		ENSP00000341619.3	P23771-1
GATA3	ENST00000481743 link	c.-264G>T	5_prime_UTR_variant	Exon 2 of 3	2		ENSP00000493486.1	A0A2R8Y2A9
GATA3	ENST00000643001 link	c.-264G>T	5_prime_UTR_variant	Exon 2 of 2			ENSP00000494284.1	A0A2R8Y4T2

Frequencies

GnomAD3 genomes

AF:

0.00117

AC:

178

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0280

Gnomad SAS

AF:

0.00332

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.00236

AC:

959

AN:

407172

Hom.:

Cov.:

AF XY:

0.00230

AC XY:

494

AN XY:

214542

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000124

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0287

Gnomad4 SAS exome

AF:

0.00207

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000217

Gnomad4 OTH exome

AF:

0.000849

GnomAD4 genome

AF:

0.00117

AC:

178

AN:

152218

Hom.:

Cov.:

AF XY:

0.00149

AC XY:

111

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0280

Gnomad4 SAS

AF:

0.00353

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000265

Hom.:

Bravo

AF:

0.00179

Asia WGS

AF:

0.00808

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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

-0.82

CADD

Benign

2.9

DANN

Benign

0.74

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over