Genetic Variant GATA3:p.Leu150Val (chr10-8058511-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001002295.2(GATA3):c.448C>G(p.Leu150Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,042 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L150I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

GATA3
NM_001002295.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.95

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 Gene-Disease associations (from GenCC):

hypoparathyroidism-deafness-renal disease syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

GATA3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA3	NM_001002295.2 link	c.448C>G	p.Leu150Val	missense_variant	Exon 3 of 6	ENST00000379328.9	NP_001002295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
GATA3	ENST00000379328.9 link	c.448C>G	p.Leu150Val	missense_variant	Exon 3 of 6	1	NM_001002295.2	ENSP00000368632.3
GATA3	ENST00000346208.4 link	c.448C>G	p.Leu150Val	missense_variant	Exon 3 of 6	1		ENSP00000341619.3
GATA3	ENST00000461472.1 link	c.112C>G	p.Leu38Val	missense_variant	Exon 1 of 3	3		ENSP00000515407.1
GATA3	ENST00000481743.2 link	c.*17C>G		downstream_gene_variant		2		ENSP00000493486.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460042

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726432

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26098

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86228

European-Finnish (FIN)

AF:

0.0000192

AC:

AN:

51980

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111750

Other (OTH)

AF:

0.00

AC:

AN:

60354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.22

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.72

.;.;D

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.96

.;D;D

M_CAP

Pathogenic

0.52

MetaRNN

Uncertain

0.58

D;D;D

MetaSVM

Pathogenic

1.0

MutationAssessor

Uncertain

2.7

M;M;M

PhyloP100

6.0

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.7

N;.;N

REVEL

Pathogenic

0.73

Sift

Uncertain

0.0060

D;.;D

Sift4G

Benign

0.084

T;.;T

Polyphen

0.74

P;P;B

Vest4

0.70

MutPred

0.25

Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);

MVP

0.89

MPC

1.8

ClinPred

0.97

GERP RS

4.6

Varity_R

0.36

gMVP

0.40

Mutation Taster

=59/41

polymorphism

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over