chr10-8055607-C-T

Position:

• chr10-8055607-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_001002295.2(GATA3):​c.-49C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0156 in 1,535,510 control chromosomes in the GnomAD database, including 232 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (14 hom., cov: 32)
  • Exomes 𝑓: 0.016 (218 hom.)
• Consequence: GATA3 NM_001002295.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.592

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 Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 10-8055607-C-T is Benign according to our data. Variant chr10-8055607-C-T is described in ClinVar as [Benign]. Clinvar id is 301115.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0114 (1741/152134) while in subpopulation NFE AF= 0.0198 (1345/67948). AF 95% confidence interval is 0.0189. There are 14 homozygotes in gnomad4. There are 776 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1741 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATA3	NM_001002295.2	c.-49C>T		5_prime_UTR_variant	2/6	ENST00000379328.9	NP_001002295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATA3	ENST00000379328.9	c.-49C>T		5_prime_UTR_variant	2/6	1	NM_001002295.2	ENSP00000368632	A1
GATA3	ENST00000346208.4	c.-49C>T		5_prime_UTR_variant	2/6	1		ENSP00000341619	P4
GATA3	ENST00000481743.2	c.-49C>T		5_prime_UTR_variant	2/3	2		ENSP00000493486
GATA3	ENST00000643001.1	c.-49C>T		5_prime_UTR_variant	2/2			ENSP00000494284

Frequencies

GnomAD3 genomes AF: 0.0115 AC: 1743 AN: 152018 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.00302

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00654

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.000195

Gnomad SAS AF: 0.00435

Gnomad FIN AF: 0.00782

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.0198

Gnomad OTH AF: 0.0101

GnomAD3 exomes AF: 0.0106 AC: 1410 AN: 133548 Hom.: 13 AF XY: 0.0109 AC XY: 796 AN XY: 73224

Gnomad AFR exome AF: 0.00313

Gnomad AMR exome AF: 0.00441

Gnomad ASJ exome AF: 0.0146

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00430

Gnomad FIN exome AF: 0.00996

Gnomad NFE exome AF: 0.0188

Gnomad OTH exome AF: 0.0105

GnomAD4 exome AF: 0.0161 AC: 22287 AN: 1383376 Hom.: 218 Cov.: 33 AF XY: 0.0159 AC XY: 10856 AN XY: 682330

Gnomad4 AFR exome AF: 0.00236

Gnomad4 AMR exome AF: 0.00452

Gnomad4 ASJ exome AF: 0.0146

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00460

Gnomad4 FIN exome AF: 0.0113

Gnomad4 NFE exome AF: 0.0186

Gnomad4 OTH exome AF: 0.0144

GnomAD4 genome AF: 0.0114 AC: 1741 AN: 152134 Hom.: 14 Cov.: 32 AF XY: 0.0104 AC XY: 776 AN XY: 74404

Gnomad4 AFR AF: 0.00301

Gnomad4 AMR AF: 0.00654

Gnomad4 ASJ AF: 0.0127

Gnomad4 EAS AF: 0.000196

Gnomad4 SAS AF: 0.00415

Gnomad4 FIN AF: 0.00782

Gnomad4 NFE AF: 0.0198

Gnomad4 OTH AF: 0.00997

Alfa AF: 0.0197 Hom.: 3

Bravo AF: 0.0103

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 28, 2017

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Hypoparathyroidism, deafness, renal disease syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	16
DANN	Uncertain	0.98

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: rs11567942; hg19: chr10-8097570;