10-8054906-CTTT-CTTTTT

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001002295.2(GATA3):​c.-370+27_-370+28dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00676 in 146,372 control chromosomes in the GnomAD database, including 15 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0068 (15 hom., cov: 24)
  • Exomes 𝑓: 0.00098 (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: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0068 (989/145354) while in subpopulation AFR AF = 0.024 (953/39762). AF 95% confidence interval is 0.0227. There are 15 homozygotes in GnomAd4. There are 437 alleles in the male GnomAd4 subpopulation. Median coverage is 24. This position passed quality control check.
• BS2: High AC in GnomAd4 at 989 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.-370+27_-370+28dupTT		intron	N/A	NP_001002295.1	P23771-2
	GATA3	NM_001441115.1		c.-369-369_-369-368dupTT		intron	N/A	NP_001428044.1
	GATA3	NM_001441116.1		c.-369-369_-369-368dupTT		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+16insTT		intron	N/A	ENSP00000368632.3	P23771-2
	GATA3	ENST00000346208.4	TSL:1	c.-370+15_-370+16insTT		intron	N/A	ENSP00000341619.3	P23771-1
	GATA3	ENST00000872595.1		c.-369-381_-369-380insTT		intron	N/A	ENSP00000542654.1

Frequencies

GnomAD3 genomes AF: 0.00681 AC: 989 AN: 145316 Hom.: 15 Cov.: 24

Gnomad AFR AF: 0.0240

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00136

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000122

Gnomad OTH AF: 0.00409

GnomAD4 exome AF: 0.000982 AC: 1 AN: 1018 Hom.: 0 Cov.: 0 AF XY: 0.00188 AC XY: 1 AN XY: 532

⚠️ 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: 20

American (AMR) AF: 0.00 AC: 0 AN: 36

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 82

East Asian (EAS) AF: 0.00538 AC: 1 AN: 186

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: 0.00 AC: 0 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), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00680 AC: 989 AN: 145354 Hom.: 15 Cov.: 24 AF XY: 0.00618 AC XY: 437 AN XY: 70676

African (AFR) AF: 0.0240 AC: 953 AN: 39762

American (AMR) AF: 0.00136 AC: 20 AN: 14678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3370

East Asian (EAS) AF: 0.00 AC: 0 AN: 4992

South Asian (SAS) AF: 0.00 AC: 0 AN: 4528

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9066

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 278

European-Non Finnish (NFE) AF: 0.000122 AC: 8 AN: 65820

Other (OTH) AF: 0.00407 AC: 8 AN: 1966

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

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs397846644; hg19: chr10-8096869;