rs2229360

Variant names:

• chr10-8074116-C-T
• rs2229360
• NM_001002295.2:c.*93C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-8074116-C-T
• chr10-8074116-C-A
• chr10-8074116-C-G

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.*93C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0239 in 1,408,806 control chromosomes in the GnomAD database, including 2,126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (234 hom., cov: 32)
  • Exomes 𝑓: 0.024 (1892 hom.)
• Consequence: GATA3 NM_001002295.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.849
• Publications: 14 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 10-8074116-C-T is Benign according to our data. Variant chr10-8074116-C-T is described in ClinVar as Benign. ClinVar VariationId is 301131.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.249 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.*93C>T		3_prime_UTR	Exon 6 of 6	NP_001002295.1	P23771-2
	GATA3	NM_001441115.1		c.*93C>T		3_prime_UTR	Exon 6 of 6	NP_001428044.1
	GATA3	NM_001441116.1		c.*93C>T		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.*93C>T		3_prime_UTR	Exon 6 of 6	ENSP00000368632.3	P23771-2
	GATA3	ENST00000346208.4	TSL:1	c.*93C>T		3_prime_UTR	Exon 6 of 6	ENSP00000341619.3	P23771-1
	GATA3	ENST00000872595.1		c.*93C>T		3_prime_UTR	Exon 7 of 7	ENSP00000542654.1

Frequencies

GnomAD3 genomes AF: 0.0262 AC: 3988 AN: 152122 Hom.: 235 Cov.: 32

Gnomad AFR AF: 0.00480

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0123

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.0702

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0112

Gnomad OTH AF: 0.0191

GnomAD4 exome AF: 0.0236 AC: 29686 AN: 1256566 Hom.: 1892 Cov.: 18 AF XY: 0.0246 AC XY: 15365 AN XY: 625492

African (AFR) AF: 0.00515 AC: 145 AN: 28156

American (AMR) AF: 0.0232 AC: 762 AN: 32906

Ashkenazi Jewish (ASJ) AF: 0.00759 AC: 167 AN: 22006

East Asian (EAS) AF: 0.275 AC: 10349 AN: 37652

South Asian (SAS) AF: 0.0545 AC: 4075 AN: 74756

European-Finnish (FIN) AF: 0.0958 AC: 4064 AN: 42436

Middle Eastern (MID) AF: 0.0125 AC: 65 AN: 5184

European-Non Finnish (NFE) AF: 0.00888 AC: 8531 AN: 960406

Other (OTH) AF: 0.0288 AC: 1528 AN: 53064

GnomAD4 genome AF: 0.0262 AC: 3989 AN: 152240 Hom.: 234 Cov.: 32 AF XY: 0.0322 AC XY: 2396 AN XY: 74424

African (AFR) AF: 0.00476 AC: 198 AN: 41572

American (AMR) AF: 0.0123 AC: 188 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0107 AC: 37 AN: 3470

East Asian (EAS) AF: 0.261 AC: 1347 AN: 5166

South Asian (SAS) AF: 0.0715 AC: 345 AN: 4828

European-Finnish (FIN) AF: 0.102 AC: 1076 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0112 AC: 759 AN: 68006

Other (OTH) AF: 0.0185 AC: 39 AN: 2112

Alfa AF: 0.0111 Hom.: 57

Bravo AF: 0.0204

Asia WGS AF: 0.120 AC: 414 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	-0.88
CADD	Benign	0.19
DANN	Benign	0.58
PhyloP100		-0.85
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: rs2229360; hg19: chr10-8116079; COSMIC: COSV60523713; COSMIC: COSV60523713;