Genetic Variant GATA3:c.-502dupA (chr10-8054743-T-TA) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001002295.2(GATA3):c.-502dupA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.10 ( 2074 hom., cov: 0)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

GATA3
NM_001002295.2 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.75

Publications

0 publications found

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:

GATA3-AS1 (HGNC:33786): (GATA3 antisense RNA 1)

GATA3-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001002295.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GATA3	NM_001002295.2	MANE Select	c.-502dupA	5_prime_UTR	Exon 1 of 6	NP_001002295.1	P23771-2
GATA3	NM_002051.3		c.-502dupA	5_prime_UTR	Exon 1 of 6	NP_002042.1	P23771-1
GATA3	NM_001441131.1		c.-502dupA	5_prime_UTR	Exon 1 of 6	NP_001428060.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GATA3	ENST00000379328.9	TSL:1 MANE Select	c.-502dupA	5_prime_UTR	Exon 1 of 6	ENSP00000368632.3	P23771-2
GATA3	ENST00000872595.1		c.-369-528dupA	intron	N/A	ENSP00000542654.1
GATA3	ENST00000481743.2	TSL:2	c.-369-528dupA	intron	N/A	ENSP00000493486.1	A0A2R8Y2A9

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

13770

AN:

132082

Hom.:

2076

Cov.:

show subpopulations

Gnomad AFR

AF:

0.342

Gnomad AMI

AF:

0.0142

Gnomad AMR

AF:

0.0431

Gnomad ASJ

AF:

0.0164

Gnomad EAS

AF:

0.0169

Gnomad SAS

AF:

0.00997

Gnomad FIN

AF:

0.0229

Gnomad MID

AF:

0.0254

Gnomad NFE

AF:

0.00782

Gnomad OTH

AF:

0.0685

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.104

AC:

13775

AN:

132068

Hom.:

2074

Cov.:

AF XY:

0.103

AC XY:

6496

AN XY:

62954

show subpopulations

African (AFR)

AF:

0.342

AC:

12267

AN:

35892

American (AMR)

AF:

0.0431

AC:

566

AN:

13130

Ashkenazi Jewish (ASJ)

AF:

0.0164

AC:

AN:

3238

East Asian (EAS)

AF:

0.0168

AC:

AN:

4476

South Asian (SAS)

AF:

0.00979

AC:

AN:

4086

European-Finnish (FIN)

AF:

0.0229

AC:

151

AN:

6586

Middle Eastern (MID)

AF:

0.0273

AC:

AN:

256

European-Non Finnish (NFE)

AF:

0.00780

AC:

482

AN:

61768

Other (OTH)

AF:

0.0682

AC:

122

AN:

1788

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

440

879

1319

1758

2198

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

256

384

512

640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.8

Mutation Taster

=294/6

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over