rs104894165

Positions:

• chr10-8073747-A-C
• chr10-8073747-A-G
• chr10-8073747-A-T

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PS1 PM2 PP3_Strong

The NM_001002295.2(GATA3):​c.1059A>C​(p.Arg353Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Pathogenicin Lovd.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GATA3 NM_001002295.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.45

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 Pathogenic. Variant got 10 ACMG points.

• PS1: Transcript NM_001002295.2 (GATA3) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in Lovd
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.977

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATA3	NM_001002295.2	c.1059A>C	p.Arg353Ser	missense_variant	6/6	ENST00000379328.9	NP_001002295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATA3	ENST00000379328.9	c.1059A>C	p.Arg353Ser	missense_variant	6/6	1	NM_001002295.2	ENSP00000368632.3
GATA3	ENST00000346208.4	c.1056A>C	p.Arg352Ser	missense_variant	6/6	1		ENSP00000341619.3
GATA3	ENST00000461472.1	c.*4A>C		3_prime_UTR_variant	3/3	3		ENSP00000515407.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.53	D
BayesDel_noAF	Pathogenic	0.52
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.96	.;.;D
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Pathogenic	0.99	.;D;D
M_CAP	Pathogenic	0.83	D
MetaRNN	Pathogenic	0.98	D;D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Uncertain	2.3	.;.;M
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-5.4	D;.;D
REVEL	Pathogenic	0.95
Sift	Uncertain	0.0010	D;.;D
Sift4G	Uncertain	0.0020	D;.;D
Polyphen		1.0	D;D;D
Vest4		0.98
MutPred		0.87		.;.;Gain of catalytic residue at R352 (P = 0.0098);
MVP		1.0
MPC		1.9
ClinPred		0.99	D
GERP RS		3.8
Varity_R		0.97
gMVP		0.99

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-8115710;