NM_001002295.2:c.-370+27_-370+28delTT

Variant names:

• chr10-8054906-CTT-C
• rs397846644
• NM_001002295.2:c.-370+27_-370+28delTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001002295.2(GATA3):​c.-370+27_-370+28delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000103 in 146,314 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000055 (0 hom., cov: 24)
  • Exomes 𝑓: 0.0069 (0 hom.)
• Consequence: GATA3 NM_001002295.2 intron
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

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+27_-370+28delTT		intron	N/A	NP_001002295.1	P23771-2
	GATA3	NM_001441115.1		c.-369-369_-369-368delTT		intron	N/A	NP_001428044.1
	GATA3	NM_001441116.1		c.-369-369_-369-368delTT		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+16_-370+17delTT		intron	N/A	ENSP00000368632.3	P23771-2
	GATA3	ENST00000346208.4	TSL:1	c.-370+16_-370+17delTT		intron	N/A	ENSP00000341619.3	P23771-1
	GATA3	ENST00000872595.1		c.-369-380_-369-379delTT		intron	N/A	ENSP00000542654.1

Frequencies

GnomAD3 genomes AF: 0.0000551 AC: 8 AN: 145300 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000297

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000552

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000152

Gnomad OTH AF: 0.000512

GnomAD4 exome AF: 0.00690 AC: 7 AN: 1014 Hom.: 0 AF XY: 0.00755 AC XY: 4 AN XY: 530

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

African (AFR) AF: 0.00 AC: 0 AN: 18

American (AMR) AF: 0.0278 AC: 1 AN: 36

Ashkenazi Jewish (ASJ) AF: 0.0244 AC: 2 AN: 82

East Asian (EAS) AF: 0.00 AC: 0 AN: 186

South Asian (SAS) AF: 0.0556 AC: 1 AN: 18

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: 0.00515 AC: 3 AN: 582

Other (OTH) AF: 0.00 AC: 0 AN: 84

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000308703), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000551 AC: 8 AN: 145300 Hom.: 0 Cov.: 24 AF XY: 0.0000425 AC XY: 3 AN XY: 70608

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

African (AFR) AF: 0.00 AC: 0 AN: 39690

American (AMR) AF: 0.00 AC: 0 AN: 14666

Ashkenazi Jewish (ASJ) AF: 0.000297 AC: 1 AN: 3370

East Asian (EAS) AF: 0.00 AC: 0 AN: 5008

South Asian (SAS) AF: 0.00 AC: 0 AN: 4542

European-Finnish (FIN) AF: 0.000552 AC: 5 AN: 9052

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 302

European-Non Finnish (NFE) AF: 0.0000152 AC: 1 AN: 65822

Other (OTH) AF: 0.000512 AC: 1 AN: 1954

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.2
Mutation Taster		=100/0	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: rs397846644; hg19: chr10-8096869;