10-8074116-C-T

Variant names:

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

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: 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=-0.88).
• 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATA3	NM_001002295.2	c.*93C>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000379328.9	NP_001002295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATA3	ENST00000379328.9	c.*93C>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_001002295.2	ENSP00000368632.3
GATA3	ENST00000346208.4	c.*93C>T		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000341619.3
GATA3	ENST00000461472.1	c.*373C>T		downstream_gene_variant		3		ENSP00000515407.1

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

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jul 05, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Hypoparathyroidism, deafness, renal disease syndrome Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

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;