NM_001002295.2:c.-370+28dupT

Variant names:

• chr10-8054906-C-CT
• rs397846644
• NM_001002295.2:c.-370+28dupT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001002295.2(GATA3):​c.-370+28dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 146,266 control chromosomes in the GnomAD database, including 3,494 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (3494 hom., cov: 24)
  • Exomes 𝑓: 0.058 (0 hom.)
• Consequence: GATA3 NM_001002295.2 intron
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 2.19
• Publications: 0 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.411 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.-370+28dupT		intron	N/A	NP_001002295.1	P23771-2
	GATA3	NM_001441115.1		c.-369-368dupT		intron	N/A	NP_001428044.1
	GATA3	NM_001441116.1		c.-369-368dupT		intron	N/A	NP_001428045.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA3	ENST00000379328.9	TSL:1 MANE Select	c.-370+15_-370+16insT		intron	N/A	ENSP00000368632.3	P23771-2
	GATA3	ENST00000346208.4	TSL:1	c.-370+15_-370+16insT		intron	N/A	ENSP00000341619.3	P23771-1
	GATA3	ENST00000872595.1		c.-369-381_-369-380insT		intron	N/A	ENSP00000542654.1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 20397 AN: 145222 Hom.: 3491 Cov.: 24

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.00336

Gnomad AMR AF: 0.0574

Gnomad ASJ AF: 0.0626

Gnomad EAS AF: 0.00459

Gnomad SAS AF: 0.0623

Gnomad FIN AF: 0.0336

Gnomad MID AF: 0.0629

Gnomad NFE AF: 0.0309

Gnomad OTH AF: 0.0973

GnomAD4 exome AF: 0.0577 AC: 58 AN: 1006 Hom.: 0 Cov.: 0 AF XY: 0.0439 AC XY: 23 AN XY: 524

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.222 AC: 4 AN: 18

American (AMR) AF: 0.139 AC: 5 AN: 36

Ashkenazi Jewish (ASJ) AF: 0.0854 AC: 7 AN: 82

East Asian (EAS) AF: 0.0435 AC: 8 AN: 184

South Asian (SAS) AF: 0.00 AC: 0 AN: 20

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.0470 AC: 27 AN: 574

Other (OTH) AF: 0.0833 AC: 7 AN: 84

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000000000555111), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.141 AC: 20418 AN: 145260 Hom.: 3494 Cov.: 24 AF XY: 0.138 AC XY: 9743 AN XY: 70630

African (AFR) AF: 0.416 AC: 16515 AN: 39712

American (AMR) AF: 0.0574 AC: 842 AN: 14674

Ashkenazi Jewish (ASJ) AF: 0.0626 AC: 211 AN: 3372

East Asian (EAS) AF: 0.00461 AC: 23 AN: 4990

South Asian (SAS) AF: 0.0621 AC: 281 AN: 4526

European-Finnish (FIN) AF: 0.0336 AC: 304 AN: 9056

Middle Eastern (MID) AF: 0.0683 AC: 19 AN: 278

European-Non Finnish (NFE) AF: 0.0309 AC: 2030 AN: 65794

Other (OTH) AF: 0.0967 AC: 190 AN: 1964

Alfa AF: 0.00725 Hom.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

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
PhyloP100		2.2
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: rs397846644; hg19: chr10-8096869;