Variant 10-8055561-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001002295.2(GATA3):c.-95G>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 0.00128 in 1,369,584 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0012 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0013 ( 12 hom. )

Consequence

GATA3
NM_001002295.2 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.888

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 10-8055561-G-T is Benign according to our data. Variant chr10-8055561-G-T is described in ClinVar as [Benign]. Clinvar id is 301111.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00118 (163/137580) while in subpopulation SAS AF= 0.0151 (61/4040). AF 95% confidence interval is 0.0121. There are 1 homozygotes in gnomad4. There are 102 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 163 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATA3	NM_001002295.2 linkuse as main transcript	c.-95G>T		5_prime_UTR_variant	2/6	ENST00000379328.9	NP_001002295.1	P23771-2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GATA3	ENST00000379328 linkuse as main transcript	c.-95G>T	5_prime_UTR_variant	2/6	1	NM_001002295.2	ENSP00000368632.3	P23771-2
GATA3	ENST00000346208 linkuse as main transcript	c.-95G>T	5_prime_UTR_variant	2/6	1		ENSP00000341619.3	P23771-1
GATA3	ENST00000481743 linkuse as main transcript	c.-95G>T	5_prime_UTR_variant	2/3	2		ENSP00000493486.1	A0A2R8Y2A9
GATA3	ENST00000643001.1 linkuse as main transcript	c.-95G>T	5_prime_UTR_variant	2/2			ENSP00000494284.1	A0A2R8Y4T2

Frequencies

GnomAD3 genomes

AF:

0.00119

AC:

163

AN:

137524

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000833

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00135

Gnomad ASJ

AF:

0.00526

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0150

Gnomad FIN

AF:

0.00182

Gnomad MID

AF:

0.0100

Gnomad NFE

AF:

0.000620

Gnomad OTH

AF:

0.00216

GnomAD4 exome

AF:

0.00129

AC:

1595

AN:

1232004

Hom.:

Cov.:

AF XY:

0.00159

AC XY:

966

AN XY:

607236

show subpopulations

Gnomad4 AFR exome

AF:

0.000541

Gnomad4 AMR exome

AF:

0.00129

Gnomad4 ASJ exome

AF:

0.00507

Gnomad4 EAS exome

AF:

0.0000307

Gnomad4 SAS exome

AF:

0.0121

Gnomad4 FIN exome

AF:

0.000992

Gnomad4 NFE exome

AF:

0.000512

Gnomad4 OTH exome

AF:

0.00220

GnomAD4 genome

AF:

0.00118

AC:

163

AN:

137580

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

102

AN XY:

67118

show subpopulations

Gnomad4 AFR

AF:

0.0000831

Gnomad4 AMR

AF:

0.00135

Gnomad4 ASJ

AF:

0.00526

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0151

Gnomad4 FIN

AF:

0.00182

Gnomad4 NFE

AF:

0.000620

Gnomad4 OTH

AF:

0.00214

Alfa

AF:

0.0000819

Hom.:

Bravo

AF:

0.000835

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

-0.50

CADD

Benign

DANN

Benign

0.95

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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