10-8073399-C-A

Variant names:

• chr10-8073399-C-A
• rs10905284
• NM_001002295.2:c.1051-340C>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.1051-340C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 151,930 control chromosomes in the GnomAD database, including 17,890 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 0.45 (17890 hom., cov: 31)
• Consequence: GATA3 NM_001002295.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120
• Publications: 15 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.574 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.1051-340C>A		intron	N/A	NP_001002295.1	P23771-2
	GATA3	NM_001441115.1		c.1051-340C>A		intron	N/A	NP_001428044.1
	GATA3	NM_001441116.1		c.1051-340C>A		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.1051-340C>A		intron	N/A	ENSP00000368632.3	P23771-2
	GATA3	ENST00000346208.4	TSL:1	c.1048-340C>A		intron	N/A	ENSP00000341619.3	P23771-1
	GATA3	ENST00000872595.1		c.1051-340C>A		intron	N/A	ENSP00000542654.1

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67883 AN: 151814 Hom.: 17892 Cov.: 31

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.489

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

GnomAD4 genome AF: 0.447 AC: 67890 AN: 151930 Hom.: 17890 Cov.: 31 AF XY: 0.449 AC XY: 33356 AN XY: 74244

African (AFR) AF: 0.150 AC: 6211 AN: 41428

American (AMR) AF: 0.457 AC: 6990 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.590 AC: 2049 AN: 3470

East Asian (EAS) AF: 0.555 AC: 2856 AN: 5148

South Asian (SAS) AF: 0.592 AC: 2847 AN: 4806

European-Finnish (FIN) AF: 0.578 AC: 6093 AN: 10542

Middle Eastern (MID) AF: 0.538 AC: 157 AN: 292

European-Non Finnish (NFE) AF: 0.575 AC: 39084 AN: 67938

Other (OTH) AF: 0.495 AC: 1044 AN: 2110

Alfa AF: 0.519 Hom.: 27249

Bravo AF: 0.422

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.1
DANN	Benign	0.55
PhyloP100		0.012
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: rs10905284; hg19: chr10-8115362;