NM_001002295.2:c.-49C>T

Variant names:

• chr10-8055607-C-T
• rs11567942
• NM_001002295.2:c.-49C>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_001002295.2(GATA3):​c.-49C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0156 in 1,535,510 control chromosomes in the GnomAD database, including 232 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (14 hom., cov: 32)
  • Exomes 𝑓: 0.016 (218 hom.)
• Consequence: GATA3 NM_001002295.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.592
• Publications: 1 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 10-8055607-C-T is Benign according to our data. Variant chr10-8055607-C-T is described in ClinVar as Benign. ClinVar VariationId is 301115.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0114 (1741/152134) while in subpopulation NFE AF = 0.0198 (1345/67948). AF 95% confidence interval is 0.0189. There are 14 homozygotes in GnomAd4. There are 776 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1741 AD gene.

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.-49C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	NP_001002295.1	P23771-2
	GATA3	NM_001002295.2	MANE Select	c.-49C>T		5_prime_UTR	Exon 2 of 6	NP_001002295.1	P23771-2
	GATA3	NM_001441115.1		c.-49C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	NP_001428044.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA3	ENST00000379328.9	TSL:1 MANE Select	c.-49C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	ENSP00000368632.3	P23771-2
	GATA3	ENST00000346208.4	TSL:1	c.-49C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	ENSP00000341619.3	P23771-1
	GATA3	ENST00000379328.9	TSL:1 MANE Select	c.-49C>T		5_prime_UTR	Exon 2 of 6	ENSP00000368632.3	P23771-2

Frequencies

GnomAD3 genomes AF: 0.0115 AC: 1743 AN: 152018 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.00302

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00654

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.000195

Gnomad SAS AF: 0.00435

Gnomad FIN AF: 0.00782

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.0198

Gnomad OTH AF: 0.0101

GnomAD2 exomes AF: 0.0106 AC: 1410 AN: 133548 AF XY: 0.0109

Gnomad AFR exome AF: 0.00313

Gnomad AMR exome AF: 0.00441

Gnomad ASJ exome AF: 0.0146

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00996

Gnomad NFE exome AF: 0.0188

Gnomad OTH exome AF: 0.0105

GnomAD4 exome AF: 0.0161 AC: 22287 AN: 1383376 Hom.: 218 Cov.: 33 AF XY: 0.0159 AC XY: 10856 AN XY: 682330

African (AFR) AF: 0.00236 AC: 74 AN: 31292

American (AMR) AF: 0.00452 AC: 160 AN: 35420

Ashkenazi Jewish (ASJ) AF: 0.0146 AC: 362 AN: 24878

East Asian (EAS) AF: 0.00 AC: 0 AN: 35578

South Asian (SAS) AF: 0.00460 AC: 362 AN: 78748

European-Finnish (FIN) AF: 0.0113 AC: 438 AN: 38816

Middle Eastern (MID) AF: 0.00304 AC: 14 AN: 4606

European-Non Finnish (NFE) AF: 0.0186 AC: 20050 AN: 1076476

Other (OTH) AF: 0.0144 AC: 827 AN: 57562

GnomAD4 genome AF: 0.0114 AC: 1741 AN: 152134 Hom.: 14 Cov.: 32 AF XY: 0.0104 AC XY: 776 AN XY: 74404

African (AFR) AF: 0.00301 AC: 125 AN: 41550

American (AMR) AF: 0.00654 AC: 100 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0127 AC: 44 AN: 3470

East Asian (EAS) AF: 0.000196 AC: 1 AN: 5114

South Asian (SAS) AF: 0.00415 AC: 20 AN: 4822

European-Finnish (FIN) AF: 0.00782 AC: 83 AN: 10618

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.0198 AC: 1345 AN: 67948

Other (OTH) AF: 0.00997 AC: 21 AN: 2106

Alfa AF: 0.0197 Hom.: 3

Bravo AF: 0.0103

Asia WGS AF: 0.00173 AC: 6 AN: 3478

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)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	16
DANN	Uncertain	0.98
PhyloP100		0.59
Mutation Taster		=300/0	polymorphism

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: rs11567942; hg19: chr10-8097570;