10-8058636-C-T

Variant names:

• chr10-8058636-C-T
• rs35508267
• NM_001002295.2:c.573C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001002295.2(GATA3):​c.573C>T​(p.Pro191Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00579 in 1,612,860 control chromosomes in the GnomAD database, including 115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0049 (12 hom., cov: 33)
  • Exomes 𝑓: 0.0059 (103 hom.)
• Consequence: GATA3 NM_001002295.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.19
• Publications: 9 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: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 10-8058636-C-T is Benign according to our data. Variant chr10-8058636-C-T is described in ClinVar as Benign. ClinVar VariationId is 301122.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.19 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00493 (751/152244) while in subpopulation SAS AF = 0.0263 (127/4824). AF 95% confidence interval is 0.0226. There are 12 homozygotes in GnomAd4. There are 404 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 751 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001002295.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA3	NM_001002295.2	MANE Select	c.573C>T	p.Pro191Pro	synonymous	Exon 3 of 6	NP_001002295.1	P23771-2
	GATA3	NM_001441115.1		c.573C>T	p.Pro191Pro	synonymous	Exon 3 of 6	NP_001428044.1
	GATA3	NM_001441116.1		c.573C>T	p.Pro191Pro	synonymous	Exon 4 of 7	NP_001428045.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA3	ENST00000379328.9	TSL:1 MANE Select	c.573C>T	p.Pro191Pro	synonymous	Exon 3 of 6	ENSP00000368632.3	P23771-2
	GATA3	ENST00000346208.4	TSL:1	c.573C>T	p.Pro191Pro	synonymous	Exon 3 of 6	ENSP00000341619.3	P23771-1
	GATA3	ENST00000872595.1		c.573C>T	p.Pro191Pro	synonymous	Exon 4 of 7	ENSP00000542654.1

Frequencies

GnomAD3 genomes AF: 0.00496 AC: 754 AN: 152126 Hom.: 12 Cov.: 33

Gnomad AFR AF: 0.000628

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00523

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.0259

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.00534

Gnomad OTH AF: 0.0124

GnomAD2 exomes AF: 0.00861 AC: 2150 AN: 249642 AF XY: 0.0102

Gnomad AFR exome AF: 0.000804

Gnomad AMR exome AF: 0.00379

Gnomad ASJ exome AF: 0.0335

Gnomad EAS exome AF: 0.000164

Gnomad FIN exome AF: 0.00155

Gnomad NFE exome AF: 0.00649

Gnomad OTH exome AF: 0.0118

GnomAD4 exome AF: 0.00588 AC: 8591 AN: 1460616 Hom.: 103 Cov.: 34 AF XY: 0.00687 AC XY: 4996 AN XY: 726702

African (AFR) AF: 0.000418 AC: 14 AN: 33478

American (AMR) AF: 0.00445 AC: 199 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0325 AC: 850 AN: 26128

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39696

South Asian (SAS) AF: 0.0294 AC: 2532 AN: 86258

European-Finnish (FIN) AF: 0.00197 AC: 103 AN: 52238

Middle Eastern (MID) AF: 0.0368 AC: 212 AN: 5768

European-Non Finnish (NFE) AF: 0.00372 AC: 4137 AN: 1111958

Other (OTH) AF: 0.00898 AC: 542 AN: 60372

GnomAD4 genome AF: 0.00493 AC: 751 AN: 152244 Hom.: 12 Cov.: 33 AF XY: 0.00543 AC XY: 404 AN XY: 74422

African (AFR) AF: 0.000626 AC: 26 AN: 41556

American (AMR) AF: 0.00523 AC: 80 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0285 AC: 99 AN: 3470

East Asian (EAS) AF: 0.000582 AC: 3 AN: 5158

South Asian (SAS) AF: 0.0263 AC: 127 AN: 4824

European-Finnish (FIN) AF: 0.00160 AC: 17 AN: 10624

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.00532 AC: 362 AN: 67992

Other (OTH) AF: 0.0118 AC: 25 AN: 2112

Alfa AF: 0.00740 Hom.: 4

Bravo AF: 0.00468

Asia WGS AF: 0.00924 AC: 32 AN: 3478

EpiCase AF: 0.00900

EpiControl AF: 0.00990

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	1	Hypoparathyroidism, deafness, renal disease syndrome (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	6.4
DANN	Benign	0.93
PhyloP100		-1.2
Mutation Taster		=99/1	polymorphism

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: rs35508267; hg19: chr10-8100599; COSMIC: COSV60523926; COSMIC: COSV60523926;