10-8055587-G-A

Variant names:

• chr10-8055587-G-A
• rs28395794
• NM_001002295.2:c.-69G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001002295.2(GATA3):​c.-69G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00154 in 1,523,606 control chromosomes in the GnomAD database, including 70 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0022 (11 hom., cov: 31)
  • Exomes 𝑓: 0.0015 (59 hom.)
• Consequence: GATA3 NM_001002295.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.28
• Publications: 3 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-AS1 (HGNC:33786): (GATA3 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 10-8055587-G-A is Benign according to our data. Variant chr10-8055587-G-A is described in ClinVar as Benign. ClinVar VariationId is 301112.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00215 (325/150850) while in subpopulation EAS AF = 0.055 (278/5052). AF 95% confidence interval is 0.0497. There are 11 homozygotes in GnomAd4. There are 188 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 325 AD gene.

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.-69G>A		5_prime_UTR	Exon 2 of 6	NP_001002295.1	P23771-2
	GATA3	NM_001441115.1		c.-69G>A		5_prime_UTR	Exon 2 of 6	NP_001428044.1
	GATA3	NM_001441116.1		c.-69G>A		5_prime_UTR	Exon 3 of 7	NP_001428045.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA3	ENST00000379328.9	TSL:1 MANE Select	c.-69G>A		5_prime_UTR	Exon 2 of 6	ENSP00000368632.3	P23771-2
	GATA3	ENST00000346208.4	TSL:1	c.-69G>A		5_prime_UTR	Exon 2 of 6	ENSP00000341619.3	P23771-1
	GATA3	ENST00000872595.1		c.-69G>A		5_prime_UTR	Exon 3 of 7	ENSP00000542654.1

Frequencies

GnomAD3 genomes AF: 0.00218 AC: 329 AN: 150746 Hom.: 11 Cov.: 31

Gnomad AFR AF: 0.000441

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000263

Gnomad ASJ AF: 0.000578

Gnomad EAS AF: 0.0554

Gnomad SAS AF: 0.00358

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00289

GnomAD4 exome AF: 0.00147 AC: 2019 AN: 1372756 Hom.: 59 Cov.: 33 AF XY: 0.00147 AC XY: 992 AN XY: 676790

African (AFR) AF: 0.0000646 AC: 2 AN: 30942

American (AMR) AF: 0.0000578 AC: 2 AN: 34602

Ashkenazi Jewish (ASJ) AF: 0.000863 AC: 21 AN: 24334

East Asian (EAS) AF: 0.0466 AC: 1638 AN: 35140

South Asian (SAS) AF: 0.00228 AC: 176 AN: 77362

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35730

Middle Eastern (MID) AF: 0.000473 AC: 2 AN: 4232

European-Non Finnish (NFE) AF: 0.0000196 AC: 21 AN: 1073220

Other (OTH) AF: 0.00275 AC: 157 AN: 57194

GnomAD4 genome AF: 0.00215 AC: 325 AN: 150850 Hom.: 11 Cov.: 31 AF XY: 0.00255 AC XY: 188 AN XY: 73684

African (AFR) AF: 0.000439 AC: 18 AN: 40970

American (AMR) AF: 0.000263 AC: 4 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.000578 AC: 2 AN: 3462

East Asian (EAS) AF: 0.0550 AC: 278 AN: 5052

South Asian (SAS) AF: 0.00338 AC: 16 AN: 4740

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10460

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67662

Other (OTH) AF: 0.00287 AC: 6 AN: 2094

Alfa AF: 0.000572 Hom.: 0

Bravo AF: 0.00290

Asia WGS AF: 0.0200 AC: 69 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Hypoparathyroidism, deafness, renal disease syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	18
DANN	Uncertain	0.97
PhyloP100		3.3
Mutation Taster		=300/0	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: rs28395794; hg19: chr10-8097550;