Genetic Variant GATA3:c.-370+28delT (chr10-8054906-CT-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001002295.2(GATA3):c.-370+28delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0797 in 146,080 control chromosomes in the GnomAD database, including 472 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.079 ( 469 hom., cov: 24)

Exomes 𝑓: 0.16 ( 3 hom. )

Consequence

GATA3
NM_001002295.2 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.19

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 -10 ACMG points.

BP6

Variant 10-8054906-CT-C is Benign according to our data. Variant chr10-8054906-CT-C is described in ClinVar as Benign. ClinVar VariationId is 301103.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0882 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.-370+28delT	intron	N/A	NP_001002295.1	P23771-2
GATA3	NM_001441115.1		c.-369-368delT	intron	N/A	NP_001428044.1
GATA3	NM_001441116.1		c.-369-368delT	intron	N/A	NP_001428045.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GATA3	ENST00000379328.9	TSL:1 MANE Select	c.-370+16delT	intron	N/A	ENSP00000368632.3	P23771-2
GATA3	ENST00000346208.4	TSL:1	c.-370+16delT	intron	N/A	ENSP00000341619.3	P23771-1
GATA3	ENST00000872595.1		c.-369-380delT	intron	N/A	ENSP00000542654.1

Frequencies

GnomAD3 genomes

AF:

0.0791

AC:

11476

AN:

145044

Hom.:

467

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0672

Gnomad AMI

AF:

0.0257

Gnomad AMR

AF:

0.0597

Gnomad ASJ

AF:

0.0657

Gnomad EAS

AF:

0.0264

Gnomad SAS

AF:

0.0459

Gnomad FIN

AF:

0.138

Gnomad MID

AF:

0.0662

Gnomad NFE

AF:

0.0901

Gnomad OTH

AF:

0.0850

GnomAD4 exome

AF:

0.157

AC:

157

AN:

1000

Hom.:

Cov.:

AF XY:

0.138

AC XY:

AN XY:

522

show subpopulations

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

African (AFR)

AF:

0.150

AC:

AN:

American (AMR)

AF:

0.0833

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.0875

AC:

AN:

East Asian (EAS)

AF:

0.154

AC:

AN:

182

South Asian (SAS)

AF:

0.100

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.250

AC:

AN:

European-Non Finnish (NFE)

AF:

0.185

AC:

106

AN:

572

Other (OTH)

AF:

0.0854

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: 0.364

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0792

AC:

11490

AN:

145080

Hom.:

469

Cov.:

AF XY:

0.0784

AC XY:

5529

AN XY:

70524

show subpopulations

African (AFR)

AF:

0.0674

AC:

2679

AN:

39740

American (AMR)

AF:

0.0596

AC:

874

AN:

14656

Ashkenazi Jewish (ASJ)

AF:

0.0657

AC:

221

AN:

3366

East Asian (EAS)

AF:

0.0265

AC:

132

AN:

4986

South Asian (SAS)

AF:

0.0462

AC:

209

AN:

4520

European-Finnish (FIN)

AF:

0.138

AC:

1247

AN:

9020

Middle Eastern (MID)

AF:

0.0683

AC:

AN:

278

European-Non Finnish (NFE)

AF:

0.0902

AC:

5920

AN:

65656

Other (OTH)

AF:

0.0845

AC:

166

AN:

1964

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

502

1005

1507

2010

2512

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

264

396

528

660

<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:

0.0377

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hypoparathyroidism, deafness, renal disease syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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10-8054906-CTTT-CTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over