10-8058669-T-C

Variant names:

• chr10-8058669-T-C
• rs2228254
• NM_001002295.2:c.606T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The ENST00000379328.9(GATA3):​c.606T>C​(p.Arg202Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00642 in 1,613,222 control chromosomes in the GnomAD database, including 603 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (292 hom., cov: 33)
  • Exomes 𝑓: 0.0036 (311 hom.)
• Consequence: GATA3 ENST00000379328.9 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.176
• Publications: 3 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 10-8058669-T-C is Benign according to our data. Variant chr10-8058669-T-C is described in ClinVar as Benign. ClinVar VariationId is 256853.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.176 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000379328.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA3	NM_001002295.2	MANE Select	c.606T>C	p.Arg202Arg	synonymous	Exon 3 of 6	NP_001002295.1
	GATA3	NM_001441115.1		c.606T>C	p.Arg202Arg	synonymous	Exon 3 of 6	NP_001428044.1
	GATA3	NM_001441116.1		c.606T>C	p.Arg202Arg	synonymous	Exon 4 of 7	NP_001428045.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA3	ENST00000379328.9	TSL:1 MANE Select	c.606T>C	p.Arg202Arg	synonymous	Exon 3 of 6	ENSP00000368632.3
	GATA3	ENST00000346208.4	TSL:1	c.606T>C	p.Arg202Arg	synonymous	Exon 3 of 6	ENSP00000341619.3
	GATA3	ENST00000461472.1	TSL:3	c.270T>C	p.Arg90Arg	synonymous	Exon 1 of 3	ENSP00000515407.1

Frequencies

GnomAD3 genomes AF: 0.0337 AC: 5128 AN: 152072 Hom.: 292 Cov.: 33

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0114

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.000324

Gnomad OTH AF: 0.0196

GnomAD2 exomes AF: 0.00860 AC: 2152 AN: 250160 AF XY: 0.00590

Gnomad AFR exome AF: 0.121

Gnomad AMR exome AF: 0.00440

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000476

Gnomad NFE exome AF: 0.000212

Gnomad OTH exome AF: 0.00327

GnomAD4 exome AF: 0.00357 AC: 5214 AN: 1461032 Hom.: 311 Cov.: 34 AF XY: 0.00302 AC XY: 2192 AN XY: 726898

African (AFR) AF: 0.127 AC: 4265 AN: 33478

American (AMR) AF: 0.00546 AC: 244 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000197 AC: 17 AN: 86258

European-Finnish (FIN) AF: 0.0000950 AC: 5 AN: 52630

Middle Eastern (MID) AF: 0.00312 AC: 18 AN: 5768

European-Non Finnish (NFE) AF: 0.000165 AC: 184 AN: 1111964

Other (OTH) AF: 0.00797 AC: 481 AN: 60384

GnomAD4 genome AF: 0.0338 AC: 5139 AN: 152190 Hom.: 292 Cov.: 33 AF XY: 0.0322 AC XY: 2398 AN XY: 74414

African (AFR) AF: 0.118 AC: 4898 AN: 41508

American (AMR) AF: 0.0114 AC: 174 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10622

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 292

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 67986

Other (OTH) AF: 0.0194 AC: 41 AN: 2114

Alfa AF: 0.0181 Hom.: 95

Bravo AF: 0.0381

Asia WGS AF: 0.00404 AC: 15 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000237

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Hypoparathyroidism, deafness, renal disease syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.2
DANN	Benign	0.64
PhyloP100		-0.18
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: rs2228254; hg19: chr10-8100632; COSMIC: COSV60516594;