rs10905277

Variant names:

• chr10-8055405-G-A
• rs10905277
• NM_001002295.2:c.-251G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001002295.2(GATA3):​c.-251G>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 0.506 in 571,986 control chromosomes in the GnomAD database, including 76,623 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (16244 hom., cov: 31)
  • Exomes 𝑓: 0.53 (60379 hom.)
• Consequence: GATA3 NM_001002295.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.431
• Publications: 16 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=-0.69).
• BP6: Variant 10-8055405-G-A is Benign according to our data. Variant chr10-8055405-G-A is described in ClinVar as Benign. ClinVar VariationId is 301109.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.626 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.-251G>A		5_prime_UTR	Exon 2 of 6	NP_001002295.1	P23771-2
	GATA3	NM_001441115.1		c.-251G>A		5_prime_UTR	Exon 2 of 6	NP_001428044.1
	GATA3	NM_001441116.1		c.-251G>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.-251G>A		5_prime_UTR	Exon 2 of 6	ENSP00000368632.3	P23771-2
	GATA3	ENST00000346208.4	TSL:1	c.-251G>A		5_prime_UTR	Exon 2 of 6	ENSP00000341619.3	P23771-1
	GATA3	ENST00000872595.1		c.-251G>A		5_prime_UTR	Exon 3 of 7	ENSP00000542654.1

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67151 AN: 151850 Hom.: 16237 Cov.: 31

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.642

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.471

GnomAD4 exome AF: 0.529 AC: 221999 AN: 420016 Hom.: 60379 Cov.: 3 AF XY: 0.535 AC XY: 118733 AN XY: 221762

African (AFR) AF: 0.228 AC: 2466 AN: 10832

American (AMR) AF: 0.424 AC: 7161 AN: 16878

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 6286 AN: 12670

East Asian (EAS) AF: 0.639 AC: 18319 AN: 28646

South Asian (SAS) AF: 0.627 AC: 28006 AN: 44640

European-Finnish (FIN) AF: 0.452 AC: 12459 AN: 27546

Middle Eastern (MID) AF: 0.480 AC: 876 AN: 1824

European-Non Finnish (NFE) AF: 0.530 AC: 134029 AN: 252700

Other (OTH) AF: 0.511 AC: 12397 AN: 24280

GnomAD4 genome AF: 0.442 AC: 67160 AN: 151970 Hom.: 16244 Cov.: 31 AF XY: 0.442 AC XY: 32870 AN XY: 74292

African (AFR) AF: 0.231 AC: 9581 AN: 41446

American (AMR) AF: 0.457 AC: 6976 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 1749 AN: 3472

East Asian (EAS) AF: 0.644 AC: 3317 AN: 5152

South Asian (SAS) AF: 0.641 AC: 3085 AN: 4816

European-Finnish (FIN) AF: 0.439 AC: 4638 AN: 10576

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.532 AC: 36102 AN: 67912

Other (OTH) AF: 0.477 AC: 1009 AN: 2114

Alfa AF: 0.497 Hom.: 22726

Bravo AF: 0.429

Asia WGS AF: 0.640 AC: 2223 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Hypoparathyroidism, deafness, renal disease syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	9.9
DANN	Benign	0.91
PhyloP100		-0.43
Mutation Taster		=300/0	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: rs10905277; hg19: chr10-8097368; COSMIC: COSV60515666; COSMIC: COSV60515666;