10-8055672-ACCAG-A

Variant names:

• chr10-8055672-ACCAG-A
• NM_001002295.2:c.20_23delAGCC

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_001002295.2(GATA3):​c.20_23delAGCC​(p.Gln7ArgfsTer4) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GATA3 NM_001002295.2 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 8.85

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 Pathogenic. Variant got 12 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 34 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 10-8055672-ACCAG-A is Pathogenic according to our data. Variant chr10-8055672-ACCAG-A is described in ClinVar as [Pathogenic]. Clinvar id is 3722884.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA3	NM_001002295.2	c.20_23delAGCC	p.Gln7ArgfsTer4	frameshift_variant	Exon 2 of 6	ENST00000379328.9	NP_001002295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATA3	ENST00000379328.9	c.20_23delAGCC	p.Gln7ArgfsTer4	frameshift_variant	Exon 2 of 6	1	NM_001002295.2	ENSP00000368632.3
GATA3	ENST00000346208.4	c.20_23delAGCC	p.Gln7ArgfsTer4	frameshift_variant	Exon 2 of 6	1		ENSP00000341619.3
GATA3	ENST00000481743.2	c.20_23delAGCC	p.Gln7ArgfsTer4	frameshift_variant	Exon 2 of 3	2		ENSP00000493486.1
GATA3	ENST00000643001.1	c.20_23delAGCC	p.Gln7ArgfsTer4	frameshift_variant	Exon 2 of 2			ENSP00000494284.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Pathogenic:1

Oct 13, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change creates a premature translational stop signal (p.Gln7Argfs*4) in the GATA3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GATA3 are known to be pathogenic (PMID: 14985365, 21242646). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GATA3-related conditions. For these reasons, this variant has been classified as Pathogenic. -

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-8097635;