Variant 10-8055405-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001002295.2(GATA3):c.-251G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 571,986 control chromosomes in the GnomAD database, including 76,623 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 16244 hom., cov: 31)

Exomes 𝑓: 0.53 ( 60379 hom. )

Consequence

GATA3
NM_001002295.2 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.431

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 10-8055405-G-A is Benign according to our data. Variant chr10-8055405-G-A is described in ClinVar as [Benign]. Clinvar id is 301109.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-8055405-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATA3	NM_001002295.2 linkuse as main transcript	c.-251G>A		5_prime_UTR_variant	2/6	ENST00000379328.9	NP_001002295.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATA3	ENST00000379328.9 linkuse as main transcript	c.-251G>A	5_prime_UTR_variant	2/6	1	NM_001002295.2	ENSP00000368632	A1	P23771-2
GATA3	ENST00000346208.4 linkuse as main transcript	c.-251G>A	5_prime_UTR_variant	2/6	1		ENSP00000341619	P4	P23771-1
GATA3	ENST00000481743.2 linkuse as main transcript	c.-251G>A	5_prime_UTR_variant	2/3	2		ENSP00000493486
GATA3	ENST00000643001.1 linkuse as main transcript	c.-251G>A	5_prime_UTR_variant	2/2			ENSP00000494284

Frequencies

GnomAD3 genomes

AF:

0.442

AC:

67151

AN:

151850

Hom.:

16237

Cov.:

show subpopulations

Gnomad AFR

AF:

0.232

Gnomad AMI

AF:

0.635

Gnomad AMR

AF:

0.456

Gnomad ASJ

AF:

0.504

Gnomad EAS

AF:

0.644

Gnomad SAS

AF:

0.642

Gnomad FIN

AF:

0.439

Gnomad MID

AF:

0.424

Gnomad NFE

AF:

0.532

Gnomad OTH

AF:

0.471

GnomAD4 exome

AF:

0.529

AC:

221999

AN:

420016

Hom.:

60379

Cov.:

AF XY:

0.535

AC XY:

118733

AN XY:

221762

show subpopulations

Gnomad4 AFR exome

AF:

0.228

Gnomad4 AMR exome

AF:

0.424

Gnomad4 ASJ exome

AF:

0.496

Gnomad4 EAS exome

AF:

0.639

Gnomad4 SAS exome

AF:

0.627

Gnomad4 FIN exome

AF:

0.452

Gnomad4 NFE exome

AF:

0.530

Gnomad4 OTH exome

AF:

0.511

GnomAD4 genome

AF:

0.442

AC:

67160

AN:

151970

Hom.:

16244

Cov.:

AF XY:

0.442

AC XY:

32870

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.231

Gnomad4 AMR

AF:

0.457

Gnomad4 ASJ

AF:

0.504

Gnomad4 EAS

AF:

0.644

Gnomad4 SAS

AF:

0.641

Gnomad4 FIN

AF:

0.439

Gnomad4 NFE

AF:

0.532

Gnomad4 OTH

AF:

0.477

Alfa

AF:

0.509

Hom.:

18136

Bravo

AF:

0.429

Asia WGS

AF:

0.640

AC:

2223

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 31, 2019	- -
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

-0.69

CADD

Benign

9.9

DANN

Benign

0.91

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