rs9746

Variant names:

• chr10-8074540-A-G
• rs9746
• NM_001002295.2:c.*517A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-8074540-A-G
• chr10-8074540-A-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.*517A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 234,226 control chromosomes in the GnomAD database, including 3,686 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2248 hom., cov: 32)
  • Exomes 𝑓: 0.18 (1438 hom.)
• Consequence: GATA3 NM_001002295.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.65
• Publications: 8 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: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 10-8074540-A-G is Benign according to our data. Variant chr10-8074540-A-G is described in ClinVar as Benign. ClinVar VariationId is 301138.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.251 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.*517A>G		3_prime_UTR	Exon 6 of 6	NP_001002295.1	P23771-2
	GATA3	NM_001441115.1		c.*517A>G		3_prime_UTR	Exon 6 of 6	NP_001428044.1
	GATA3	NM_001441116.1		c.*517A>G		3_prime_UTR	Exon 7 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.*517A>G		3_prime_UTR	Exon 6 of 6	ENSP00000368632.3	P23771-2
	GATA3	ENST00000346208.4	TSL:1	c.*517A>G		3_prime_UTR	Exon 6 of 6	ENSP00000341619.3	P23771-1
	GATA3	ENST00000955812.1		c.*517A>G		3_prime_UTR	Exon 6 of 6	ENSP00000625871.1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25505 AN: 152026 Hom.: 2250 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.162

GnomAD4 exome AF: 0.177 AC: 14555 AN: 82080 Hom.: 1438 Cov.: 0 AF XY: 0.178 AC XY: 6726 AN XY: 37792

African (AFR) AF: 0.202 AC: 793 AN: 3932

American (AMR) AF: 0.140 AC: 358 AN: 2556

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 1085 AN: 5148

East Asian (EAS) AF: 0.273 AC: 3123 AN: 11424

South Asian (SAS) AF: 0.198 AC: 142 AN: 718

European-Finnish (FIN) AF: 0.188 AC: 35 AN: 186

Middle Eastern (MID) AF: 0.209 AC: 103 AN: 492

European-Non Finnish (NFE) AF: 0.153 AC: 7751 AN: 50794

Other (OTH) AF: 0.171 AC: 1165 AN: 6830

GnomAD4 genome AF: 0.168 AC: 25509 AN: 152146 Hom.: 2248 Cov.: 32 AF XY: 0.169 AC XY: 12592 AN XY: 74382

African (AFR) AF: 0.194 AC: 8055 AN: 41516

American (AMR) AF: 0.123 AC: 1888 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 752 AN: 3470

East Asian (EAS) AF: 0.262 AC: 1354 AN: 5164

South Asian (SAS) AF: 0.212 AC: 1018 AN: 4808

European-Finnish (FIN) AF: 0.189 AC: 1994 AN: 10568

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.145 AC: 9844 AN: 68000

Other (OTH) AF: 0.159 AC: 336 AN: 2116

Alfa AF: 0.157 Hom.: 2273

Bravo AF: 0.166

Asia WGS AF: 0.187 AC: 650 AN: 3476

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	-0.81
CADD	Benign	9.4
DANN	Benign	0.81
PhyloP100		2.7
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs9746;

hg19: chr10-8116503;