10-8066629-T-C

Variant names:

• chr10-8066629-T-C
• rs569421
• NM_001002295.2:c.924+2491T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001002295.2(GATA3):​c.924+2491T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 152,004 control chromosomes in the GnomAD database, including 7,055 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.29 (7055 hom., cov: 31)
• Consequence: GATA3 NM_001002295.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0690
• Publications: 13 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA3	NM_001002295.2	c.924+2491T>C		intron_variant	Intron 4 of 5	ENST00000379328.9	NP_001002295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATA3	ENST00000379328.9	c.924+2491T>C		intron_variant	Intron 4 of 5	1	NM_001002295.2	ENSP00000368632.3
GATA3	ENST00000346208.4	c.921+2491T>C		intron_variant	Intron 4 of 5	1		ENSP00000341619.3
GATA3	ENST00000461472.1	c.443-2844T>C		intron_variant	Intron 1 of 2	3		ENSP00000515407.1

Frequencies

GnomAD3 genomes AF: 0.290 AC: 43996 AN: 151886 Hom.: 7044 Cov.: 31

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.265

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.290 AC: 44031 AN: 152004 Hom.: 7055 Cov.: 31 AF XY: 0.290 AC XY: 21543 AN XY: 74306

African (AFR) AF: 0.435 AC: 18002 AN: 41400

American (AMR) AF: 0.180 AC: 2745 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1102 AN: 3460

East Asian (EAS) AF: 0.272 AC: 1411 AN: 5178

South Asian (SAS) AF: 0.266 AC: 1283 AN: 4818

European-Finnish (FIN) AF: 0.280 AC: 2960 AN: 10568

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.230 AC: 15631 AN: 67990

Other (OTH) AF: 0.261 AC: 550 AN: 2106

Alfa AF: 0.250 Hom.: 22030

Bravo AF: 0.292

Asia WGS AF: 0.249 AC: 862 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.0
DANN	Benign	0.64
PhyloP100		-0.069
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs569421; hg19: chr10-8108592;