10-8055608-G-T

Variant names:

• chr10-8055608-G-T
• rs554517990
• NM_001002295.2:c.-48G>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.-48G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000549 in 1,521,422 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0031 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00028 (1 hom.)
• Consequence: GATA3 NM_001002295.2 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.696
• 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=-0.38).
• BP6: Variant 10-8055608-G-T is Benign according to our data. Variant chr10-8055608-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 301116.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00308 (454/147362) while in subpopulation AFR AF = 0.0107 (423/39450). AF 95% confidence interval is 0.00988. There are 1 homozygotes in GnomAd4. There are 208 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 454 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.-48G>T		5_prime_UTR	Exon 2 of 6	NP_001002295.1	P23771-2
	GATA3	NM_001441115.1		c.-48G>T		5_prime_UTR	Exon 2 of 6	NP_001428044.1
	GATA3	NM_001441116.1		c.-48G>T		5_prime_UTR	Exon 3 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.-48G>T		5_prime_UTR	Exon 2 of 6	ENSP00000368632.3	P23771-2
	GATA3	ENST00000346208.4	TSL:1	c.-48G>T		5_prime_UTR	Exon 2 of 6	ENSP00000341619.3	P23771-1
	GATA3	ENST00000872595.1		c.-48G>T		5_prime_UTR	Exon 3 of 7	ENSP00000542654.1

Frequencies

GnomAD3 genomes AF: 0.00306 AC: 451 AN: 147274 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0107

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00174

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00329

Gnomad NFE AF: 0.0000150

Gnomad OTH AF: 0.00149

GnomAD2 exomes AF: 0.000675 AC: 87 AN: 128930 AF XY: 0.000507

Gnomad AFR exome AF: 0.0136

Gnomad AMR exome AF: 0.000255

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000617

Gnomad OTH exome AF: 0.000515

GnomAD4 exome AF: 0.000278 AC: 382 AN: 1374060 Hom.: 1 Cov.: 33 AF XY: 0.000230 AC XY: 156 AN XY: 677672

African (AFR) AF: 0.0105 AC: 323 AN: 30792

American (AMR) AF: 0.000434 AC: 15 AN: 34568

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24596

East Asian (EAS) AF: 0.00 AC: 0 AN: 34628

South Asian (SAS) AF: 0.00 AC: 0 AN: 77300

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38450

Middle Eastern (MID) AF: 0.000659 AC: 3 AN: 4550

European-Non Finnish (NFE) AF: 0.00000839 AC: 9 AN: 1072116

Other (OTH) AF: 0.000561 AC: 32 AN: 57060

GnomAD4 genome AF: 0.00308 AC: 454 AN: 147362 Hom.: 1 Cov.: 32 AF XY: 0.00289 AC XY: 208 AN XY: 71896

African (AFR) AF: 0.0107 AC: 423 AN: 39450

American (AMR) AF: 0.00173 AC: 26 AN: 14994

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3416

East Asian (EAS) AF: 0.00 AC: 0 AN: 4962

South Asian (SAS) AF: 0.00 AC: 0 AN: 4608

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9998

Middle Eastern (MID) AF: 0.00355 AC: 1 AN: 282

European-Non Finnish (NFE) AF: 0.0000150 AC: 1 AN: 66724

Other (OTH) AF: 0.00147 AC: 3 AN: 2036

Alfa AF: 0.0000697 Hom.: 0

Bravo AF: 0.00334

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely 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	-0.38
CADD	Benign	17
DANN	Benign	0.96
PhyloP100		0.70
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: rs554517990; hg19: chr10-8097571;