rs10905278

Variant names:

• chr10-8057860-G-A
• rs10905278
• NM_001002295.2:c.242-445G>A

Variant summary

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

The NM_001002295.2(GATA3):​c.242-445G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0359 in 152,222 control chromosomes in the GnomAD database, including 135 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 0.036 (135 hom., cov: 32)
• Consequence: GATA3 NM_001002295.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.322
• Publications: 2 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: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0535 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA3	NM_001002295.2	MANE Select	c.242-445G>A		intron	N/A	NP_001002295.1
	GATA3	NM_001441115.1		c.242-445G>A		intron	N/A	NP_001428044.1
	GATA3	NM_001441116.1		c.242-445G>A		intron	N/A	NP_001428045.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA3	ENST00000379328.9	TSL:1 MANE Select	c.242-445G>A		intron	N/A	ENSP00000368632.3
	GATA3	ENST00000346208.4	TSL:1	c.242-445G>A		intron	N/A	ENSP00000341619.3
	GATA3	ENST00000481743.2	TSL:2	c.242-445G>A		intron	N/A	ENSP00000493486.1

Frequencies

GnomAD3 genomes AF: 0.0360 AC: 5471 AN: 152104 Hom.: 135 Cov.: 32

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0454

Gnomad ASJ AF: 0.0239

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00935

Gnomad FIN AF: 0.0358

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0550

Gnomad OTH AF: 0.0379

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

GnomAD4 genome AF: 0.0359 AC: 5469 AN: 152222 Hom.: 135 Cov.: 32 AF XY: 0.0356 AC XY: 2648 AN XY: 74432

African (AFR) AF: 0.0104 AC: 432 AN: 41574

American (AMR) AF: 0.0453 AC: 693 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0239 AC: 83 AN: 3466

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5166

South Asian (SAS) AF: 0.00936 AC: 45 AN: 4808

European-Finnish (FIN) AF: 0.0358 AC: 380 AN: 10600

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0550 AC: 3739 AN: 68000

Other (OTH) AF: 0.0375 AC: 79 AN: 2104

Alfa AF: 0.0471 Hom.: 255

Bravo AF: 0.0349

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.4
DANN	Benign	0.63
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism

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: rs10905278; hg19: chr10-8099823;