rs1058240

Variant names:

• chr10-8074635-G-A
• rs1058240
• NM_001002295.2:c.*612G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-8074635-G-A
• chr10-8074635-G-C

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.*612G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.824 in 233,718 control chromosomes in the GnomAD database, including 79,772 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.81 (50536 hom., cov: 34)
  • Exomes 𝑓: 0.84 (29236 hom.)
• Consequence: GATA3 NM_001002295.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.463
• Publications: 24 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 10-8074635-G-A is Benign according to our data. Variant chr10-8074635-G-A is described in ClinVar as Benign. ClinVar VariationId is 301140.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.954 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.*612G>A		3_prime_UTR	Exon 6 of 6	NP_001002295.1
	GATA3	NM_001441115.1		c.*612G>A		3_prime_UTR	Exon 6 of 6	NP_001428044.1
	GATA3	NM_001441116.1		c.*612G>A		3_prime_UTR	Exon 7 of 7	NP_001428045.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA3	ENST00000379328.9	TSL:1 MANE Select	c.*612G>A		3_prime_UTR	Exon 6 of 6	ENSP00000368632.3
	GATA3	ENST00000346208.4	TSL:1	c.*612G>A		3_prime_UTR	Exon 6 of 6	ENSP00000341619.3
	GATA3	ENST00000955812.1		c.*612G>A		3_prime_UTR	Exon 6 of 6	ENSP00000625871.1

Frequencies

GnomAD3 genomes AF: 0.814 AC: 123734 AN: 152098 Hom.: 50495 Cov.: 34

Gnomad AFR AF: 0.763

Gnomad AMI AF: 0.896

Gnomad AMR AF: 0.861

Gnomad ASJ AF: 0.905

Gnomad EAS AF: 0.977

Gnomad SAS AF: 0.931

Gnomad FIN AF: 0.832

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.803

Gnomad OTH AF: 0.829

GnomAD4 exome AF: 0.844 AC: 68779 AN: 81502 Hom.: 29236 Cov.: 0 AF XY: 0.844 AC XY: 31688 AN XY: 37526

African (AFR) AF: 0.762 AC: 2970 AN: 3900

American (AMR) AF: 0.886 AC: 2215 AN: 2500

Ashkenazi Jewish (ASJ) AF: 0.898 AC: 4602 AN: 5124

East Asian (EAS) AF: 0.983 AC: 11212 AN: 11402

South Asian (SAS) AF: 0.919 AC: 645 AN: 702

European-Finnish (FIN) AF: 0.817 AC: 397 AN: 486

Middle Eastern (MID) AF: 0.879 AC: 436 AN: 496

European-Non Finnish (NFE) AF: 0.812 AC: 40663 AN: 50108

Other (OTH) AF: 0.831 AC: 5639 AN: 6784

GnomAD4 genome AF: 0.814 AC: 123832 AN: 152216 Hom.: 50536 Cov.: 34 AF XY: 0.818 AC XY: 60855 AN XY: 74434

African (AFR) AF: 0.763 AC: 31673 AN: 41514

American (AMR) AF: 0.862 AC: 13187 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.905 AC: 3143 AN: 3472

East Asian (EAS) AF: 0.977 AC: 5067 AN: 5188

South Asian (SAS) AF: 0.931 AC: 4497 AN: 4828

European-Finnish (FIN) AF: 0.832 AC: 8807 AN: 10586

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.803 AC: 54623 AN: 68004

Other (OTH) AF: 0.831 AC: 1756 AN: 2114

Alfa AF: 0.814 Hom.: 105614

Bravo AF: 0.817

Asia WGS AF: 0.935 AC: 3250 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.95
CADD	Benign	0.013
DANN	Benign	0.53
PhyloP100		-0.46
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: rs1058240; hg19: chr10-8116598;