10-8055596-C-T

Position:

• chr10-8055596-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001002295.2(GATA3):​c.-60C>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 0.00772 in 1,531,068 control chromosomes in the GnomAD database, including 805 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.040 (411 hom., cov: 31)
  • Exomes 𝑓: 0.0042 (394 hom.)
• Consequence: GATA3 NM_001002295.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.51

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=-0.31).
• BP6: Variant 10-8055596-C-T is Benign according to our data. Variant chr10-8055596-C-T is described in ClinVar as [Benign]. Clinvar id is 301113.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATA3	NM_001002295.2	c.-60C>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.-60C>T		5_prime_UTR_variant	2/6	1	NM_001002295.2	ENSP00000368632	A1
GATA3	ENST00000346208.4	c.-60C>T		5_prime_UTR_variant	2/6	1		ENSP00000341619	P4
GATA3	ENST00000481743.2	c.-60C>T		5_prime_UTR_variant	2/3	2		ENSP00000493486
GATA3	ENST00000643001.1	c.-60C>T		5_prime_UTR_variant	2/2			ENSP00000494284

Frequencies

GnomAD3 genomes AF: 0.0401 AC: 6080 AN: 151782 Hom.: 410 Cov.: 31

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0143

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000624

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.000427

Gnomad OTH AF: 0.0259

GnomAD4 exome AF: 0.00416 AC: 5734 AN: 1379172 Hom.: 394 Cov.: 33 AF XY: 0.00352 AC XY: 2396 AN XY: 680180

Gnomad4 AFR exome AF: 0.151

Gnomad4 AMR exome AF: 0.00699

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000268

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000179

Gnomad4 OTH exome AF: 0.00973

GnomAD4 genome AF: 0.0401 AC: 6089 AN: 151896 Hom.: 411 Cov.: 31 AF XY: 0.0382 AC XY: 2839 AN XY: 74248

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.0143

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.0257

Alfa AF: 0.0348 Hom.: 36

Asia WGS AF: 0.00664 AC: 24 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 21, 2018	- -
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	-0.31
CADD	Benign	20
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: rs11567887; hg19: chr10-8097559;