Variant 10-8069446-C-T 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.925-27C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.774 in 1,606,638 control chromosomes in the GnomAD database, including 483,999 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.77 ( 45354 hom., cov: 26)

Exomes 𝑓: 0.77 ( 438645 hom. )

Consequence

GATA3
NM_001002295.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.69

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

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 3 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 10-8069446-C-T is Benign according to our data. Variant chr10-8069446-C-T is described in ClinVar as [Benign]. Clinvar id is 1234255.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA3	NM_001002295.2 link	c.925-27C>T		intron_variant	Intron 4 of 5	ENST00000379328.9	NP_001002295.1	P23771-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GATA3	ENST00000379328.9 link	c.925-27C>T	intron_variant	Intron 4 of 5	1	NM_001002295.2	ENSP00000368632.3	P23771-2
GATA3	ENST00000346208.4 link	c.922-27C>T	intron_variant	Intron 4 of 5	1		ENSP00000341619.3	P23771-1
GATA3	ENST00000461472.1 link	c.443-27C>T	intron_variant	Intron 1 of 2	3		ENSP00000515407.1	A0A994J6H6

Frequencies

GnomAD3 genomes

AF:

0.774

AC:

116869

AN:

150936

Hom.:

45328

Cov.:

show subpopulations

Gnomad AFR

AF:

0.733

Gnomad AMI

AF:

0.876

Gnomad AMR

AF:

0.831

Gnomad ASJ

AF:

0.841

Gnomad EAS

AF:

0.956

Gnomad SAS

AF:

0.847

Gnomad FIN

AF:

0.797

Gnomad MID

AF:

0.823

Gnomad NFE

AF:

0.759

Gnomad OTH

AF:

0.791

GnomAD3 exomes

AF:

0.806

AC:

202332

AN:

251036

Hom.:

82029

AF XY:

0.806

AC XY:

109416

AN XY:

135686

show subpopulations

Gnomad AFR exome

AF:

0.733

Gnomad AMR exome

AF:

0.876

Gnomad ASJ exome

AF:

0.836

Gnomad EAS exome

AF:

0.953

Gnomad SAS exome

AF:

0.833

Gnomad FIN exome

AF:

0.798

Gnomad NFE exome

AF:

0.764

Gnomad OTH exome

AF:

0.795

GnomAD4 exome

AF:

0.774

AC:

1127126

AN:

1455586

Hom.:

438645

Cov.:

AF XY:

0.777

AC XY:

562880

AN XY:

724524

show subpopulations

Gnomad4 AFR exome

AF:

0.733

Gnomad4 AMR exome

AF:

0.872

Gnomad4 ASJ exome

AF:

0.834

Gnomad4 EAS exome

AF:

0.957

Gnomad4 SAS exome

AF:

0.833

Gnomad4 FIN exome

AF:

0.797

Gnomad4 NFE exome

AF:

0.757

Gnomad4 OTH exome

AF:

0.789

GnomAD4 genome

AF:

0.774

AC:

116943

AN:

151052

Hom.:

45354

Cov.:

AF XY:

0.778

AC XY:

57400

AN XY:

73732

show subpopulations

Gnomad4 AFR

AF:

0.732

Gnomad4 AMR

AF:

0.831

Gnomad4 ASJ

AF:

0.841

Gnomad4 EAS

AF:

0.956

Gnomad4 SAS

AF:

0.847

Gnomad4 FIN

AF:

0.797

Gnomad4 NFE

AF:

0.759

Gnomad4 OTH

AF:

0.794

Alfa

AF:

0.770

Hom.:

41968

Bravo

AF:

0.776

Asia WGS

AF:

0.875

AC:

3041

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

Jun 22, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Hypoparathyroidism, deafness, renal disease syndrome

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.091

DANN

Benign

0.56

BranchPoint Hunter

3.0

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