10-8055405-G-A

Variant names:

• chr10-8055405-G-A
• rs10905277
• NM_001002295.2:c.-251G>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001002295.2(GATA3):​c.-251G>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 0.506 in 571,986 control chromosomes in the GnomAD database, including 76,623 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (16244 hom., cov: 31)
  • Exomes 𝑓: 0.53 (60379 hom.)
• Consequence: GATA3 NM_001002295.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.431

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=-0.69).
• BP6: Variant 10-8055405-G-A is Benign according to our data. Variant chr10-8055405-G-A is described in ClinVar as [Benign]. Clinvar id is 301109.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-8055405-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA3	NM_001002295.2	c.-251G>A		5_prime_UTR_variant	Exon 2 of 6	ENST00000379328.9	NP_001002295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATA3	ENST00000379328	c.-251G>A		5_prime_UTR_variant	Exon 2 of 6	1	NM_001002295.2	ENSP00000368632.3
GATA3	ENST00000346208	c.-251G>A		5_prime_UTR_variant	Exon 2 of 6	1		ENSP00000341619.3
GATA3	ENST00000481743	c.-251G>A		5_prime_UTR_variant	Exon 2 of 3	2		ENSP00000493486.1
GATA3	ENST00000643001	c.-251G>A		5_prime_UTR_variant	Exon 2 of 2			ENSP00000494284.1

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67151 AN: 151850 Hom.: 16237 Cov.: 31

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.642

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.471

GnomAD4 exome AF: 0.529 AC: 221999 AN: 420016 Hom.: 60379 Cov.: 3 AF XY: 0.535 AC XY: 118733 AN XY: 221762

Gnomad4 AFR exome AF: 0.228

Gnomad4 AMR exome AF: 0.424

Gnomad4 ASJ exome AF: 0.496

Gnomad4 EAS exome AF: 0.639

Gnomad4 SAS exome AF: 0.627

Gnomad4 FIN exome AF: 0.452

Gnomad4 NFE exome AF: 0.530

Gnomad4 OTH exome AF: 0.511

GnomAD4 genome AF: 0.442 AC: 67160 AN: 151970 Hom.: 16244 Cov.: 31 AF XY: 0.442 AC XY: 32870 AN XY: 74292

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.457

Gnomad4 ASJ AF: 0.504

Gnomad4 EAS AF: 0.644

Gnomad4 SAS AF: 0.641

Gnomad4 FIN AF: 0.439

Gnomad4 NFE AF: 0.532

Gnomad4 OTH AF: 0.477

Alfa AF: 0.509 Hom.: 18136

Bravo AF: 0.429

Asia WGS AF: 0.640 AC: 2223 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Mar 31, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Hypoparathyroidism, deafness, renal disease syndrome Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.69
CADD	Benign	9.9
DANN	Benign	0.91

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: rs10905277; hg19: chr10-8097368; COSMIC: COSV60515666; COSMIC: COSV60515666;