10-8055665-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001002295.2(GATA3):c.10A>G(p.Thr4Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,404,162 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: GATA3 NM_001002295.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.60

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08573526).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATA3	NM_001002295.2	c.10A>G	p.Thr4Ala	missense_variant	2/6	ENST00000379328.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATA3	ENST00000379328.9	c.10A>G	p.Thr4Ala	missense_variant	2/6	1	NM_001002295.2	A1
GATA3	ENST00000346208.4	c.10A>G	p.Thr4Ala	missense_variant	2/6	1		P4
GATA3	ENST00000481743.2	c.10A>G	p.Thr4Ala	missense_variant	2/3	2
GATA3	ENST00000643001.1	c.10A>G	p.Thr4Ala	missense_variant	2/2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000129 AC: 2 AN: 155488 Hom.: 0 AF XY: 0.0000239 AC XY: 2 AN XY: 83702

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000237

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000214 AC: 3 AN: 1404162 Hom.: 0 Cov.: 33 AF XY: 0.00000288 AC XY: 2 AN XY: 693370

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000119

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Oct 07, 2022

In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	0.0084	T
BayesDel_noAF	Benign	-0.23
Cadd	Benign	21
Dann	Benign	0.77
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.83	T;T;.;T;T
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.086	T;T;T;T;T
MetaSVM	Benign	-0.31	T
MutationTaster	Benign	0.83	N;N
PrimateAI	Uncertain	0.65	T
Polyphen		0.0, 0.0040	.;.;B;B;B
Vest4		0.039, 0.037
MutPred		0.15		Loss of glycosylation at T4 (P = 0.0374);Loss of glycosylation at T4 (P = 0.0374);Loss of glycosylation at T4 (P = 0.0374);Loss of glycosylation at T4 (P = 0.0374);Loss of glycosylation at T4 (P = 0.0374);
MVP		0.55
MPC		0.73
ClinPred		0.058	T
GERP RS		4.6
Varity_R		0.070
gMVP		0.29

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

LitVar

Other links and lift over

dbSNP: rs1274932119; hg19: chr10-8097628;