10-8055587-G-A

Position:

• chr10-8055587-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001002295.2(GATA3):​c.-69G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00154 in 1,523,606 control chromosomes in the GnomAD database, including 70 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0022 (11 hom., cov: 31)
  • Exomes 𝑓: 0.0015 (59 hom.)
• Consequence: GATA3 NM_001002295.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.28

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 10-8055587-G-A is Benign according to our data. Variant chr10-8055587-G-A is described in ClinVar as [Benign]. Clinvar id is 301112.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00215 (325/150850) while in subpopulation EAS AF= 0.055 (278/5052). AF 95% confidence interval is 0.0497. There are 11 homozygotes in gnomad4. There are 188 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 325 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATA3	NM_001002295.2	c.-69G>A		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.-69G>A		5_prime_UTR_variant	2/6	1	NM_001002295.2	ENSP00000368632	A1
GATA3	ENST00000346208.4	c.-69G>A		5_prime_UTR_variant	2/6	1		ENSP00000341619	P4
GATA3	ENST00000481743.2	c.-69G>A		5_prime_UTR_variant	2/3	2		ENSP00000493486
GATA3	ENST00000643001.1	c.-69G>A		5_prime_UTR_variant	2/2			ENSP00000494284

Frequencies

GnomAD3 genomes AF: 0.00218 AC: 329 AN: 150746 Hom.: 11 Cov.: 31

Gnomad AFR AF: 0.000441

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000263

Gnomad ASJ AF: 0.000578

Gnomad EAS AF: 0.0554

Gnomad SAS AF: 0.00358

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00289

GnomAD4 exome AF: 0.00147 AC: 2019 AN: 1372756 Hom.: 59 Cov.: 33 AF XY: 0.00147 AC XY: 992 AN XY: 676790

Gnomad4 AFR exome AF: 0.0000646

Gnomad4 AMR exome AF: 0.0000578

Gnomad4 ASJ exome AF: 0.000863

Gnomad4 EAS exome AF: 0.0466

Gnomad4 SAS exome AF: 0.00228

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000196

Gnomad4 OTH exome AF: 0.00275

GnomAD4 genome AF: 0.00215 AC: 325 AN: 150850 Hom.: 11 Cov.: 31 AF XY: 0.00255 AC XY: 188 AN XY: 73684

Gnomad4 AFR AF: 0.000439

Gnomad4 AMR AF: 0.000263

Gnomad4 ASJ AF: 0.000578

Gnomad4 EAS AF: 0.0550

Gnomad4 SAS AF: 0.00338

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000148

Gnomad4 OTH AF: 0.00287

Alfa AF: 0.000572 Hom.: 0

Bravo AF: 0.00290

Asia WGS AF: 0.0200 AC: 69 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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	-0.51
CADD	Benign	18
DANN	Uncertain	0.97

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: rs28395794; hg19: chr10-8097550;