NM_001002295.2:c.778+2456A>C

Variant names:

• chr10-8061297-A-C
• rs444762
• NM_001002295.2:c.778+2456A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001002295.2(GATA3):​c.778+2456A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 152,036 control chromosomes in the GnomAD database, including 34,201 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.67 (34201 hom., cov: 32)
• Consequence: GATA3 NM_001002295.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.225
• Publications: 5 publications found

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]

GATA3 Gene-Disease associations (from GenCC):

• hypoparathyroidism-deafness-renal disease syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001002295.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA3	NM_001002295.2	MANE Select	c.778+2456A>C		intron	N/A	NP_001002295.1	P23771-2
	GATA3	NM_001441115.1		c.778+2456A>C		intron	N/A	NP_001428044.1
	GATA3	NM_001441116.1		c.778+2456A>C		intron	N/A	NP_001428045.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA3	ENST00000379328.9	TSL:1 MANE Select	c.778+2456A>C		intron	N/A	ENSP00000368632.3	P23771-2
	GATA3	ENST00000346208.4	TSL:1	c.778+2456A>C		intron	N/A	ENSP00000341619.3	P23771-1
	GATA3	ENST00000872595.1		c.778+2456A>C		intron	N/A	ENSP00000542654.1

Frequencies

GnomAD3 genomes AF: 0.671 AC: 101908 AN: 151918 Hom.: 34178 Cov.: 32

Gnomad AFR AF: 0.682

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.679

Gnomad OTH AF: 0.661

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

GnomAD4 genome AF: 0.671 AC: 101975 AN: 152036 Hom.: 34201 Cov.: 32 AF XY: 0.669 AC XY: 49714 AN XY: 74332

African (AFR) AF: 0.681 AC: 28248 AN: 41472

American (AMR) AF: 0.603 AC: 9202 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.669 AC: 2321 AN: 3470

East Asian (EAS) AF: 0.695 AC: 3593 AN: 5172

South Asian (SAS) AF: 0.757 AC: 3648 AN: 4820

European-Finnish (FIN) AF: 0.629 AC: 6642 AN: 10568

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.679 AC: 46135 AN: 67954

Other (OTH) AF: 0.665 AC: 1403 AN: 2110

Alfa AF: 0.675 Hom.: 12016

Bravo AF: 0.664

Asia WGS AF: 0.748 AC: 2602 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.8
DANN	Benign	0.63
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs444762; hg19: chr10-8103260;