10-8054906-C-CT

Position:

• chr10-8054906-C-CT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001002295.2(GATA3):​c.-370+28dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 146,266 control chromosomes in the GnomAD database, including 3,494 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (3494 hom., cov: 24)
  • Exomes 𝑓: 0.058 (0 hom.)
• Consequence: GATA3 NM_001002295.2 intron
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 2.19

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATA3	NM_001002295.2	c.-370+28dup		intron_variant		ENST00000379328.9	NP_001002295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATA3	ENST00000379328.9	c.-370+28dup		intron_variant		1	NM_001002295.2	ENSP00000368632	A1
GATA3	ENST00000346208.4	c.-370+28dup		intron_variant		1		ENSP00000341619	P4
GATA3	ENST00000481743.2	c.-369-368dup		intron_variant		2		ENSP00000493486
GATA3	ENST00000643001.1	c.-369-368dup		intron_variant				ENSP00000494284

Frequencies

GnomAD3 genomes AF: 0.140 AC: 20397 AN: 145222 Hom.: 3491 Cov.: 24

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.00336

Gnomad AMR AF: 0.0574

Gnomad ASJ AF: 0.0626

Gnomad EAS AF: 0.00459

Gnomad SAS AF: 0.0623

Gnomad FIN AF: 0.0336

Gnomad MID AF: 0.0629

Gnomad NFE AF: 0.0309

Gnomad OTH AF: 0.0973

GnomAD4 exome AF: 0.0577 AC: 58 AN: 1006 Hom.: 0 Cov.: 0 AF XY: 0.0439 AC XY: 23 AN XY: 524

Gnomad4 AFR exome AF: 0.222

Gnomad4 AMR exome AF: 0.139

Gnomad4 ASJ exome AF: 0.0854

Gnomad4 EAS exome AF: 0.0435

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0470

Gnomad4 OTH exome AF: 0.0833

GnomAD4 genome AF: 0.141 AC: 20418 AN: 145260 Hom.: 3494 Cov.: 24 AF XY: 0.138 AC XY: 9743 AN XY: 70630

Gnomad4 AFR AF: 0.416

Gnomad4 AMR AF: 0.0574

Gnomad4 ASJ AF: 0.0626

Gnomad4 EAS AF: 0.00461

Gnomad4 SAS AF: 0.0621

Gnomad4 FIN AF: 0.0336

Gnomad4 NFE AF: 0.0309

Gnomad4 OTH AF: 0.0967

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Hypoparathyroidism, deafness, renal disease syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs397846644; hg19: chr10-8096869;