NM_001002295.2:c.-370+28delT

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001002295.2(GATA3):​c.-370+28delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0797 in 146,080 control chromosomes in the GnomAD database, including 472 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.079 (469 hom., cov: 24)
  • Exomes 𝑓: 0.16 (3 hom.)
• Consequence: GATA3 NM_001002295.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 10-8054906-CT-C is Benign according to our data. Variant chr10-8054906-CT-C is described in ClinVar as Benign. ClinVar VariationId is 301103.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0882 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+28delT		intron	N/A	NP_001002295.1	P23771-2
	GATA3	NM_001441115.1		c.-369-368delT		intron	N/A	NP_001428044.1
	GATA3	NM_001441116.1		c.-369-368delT		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+16delT		intron	N/A	ENSP00000368632.3	P23771-2
	GATA3	ENST00000346208.4	TSL:1	c.-370+16delT		intron	N/A	ENSP00000341619.3	P23771-1
	GATA3	ENST00000872595.1		c.-369-380delT		intron	N/A	ENSP00000542654.1

Frequencies

GnomAD3 genomes AF: 0.0791 AC: 11476 AN: 145044 Hom.: 467 Cov.: 24

Gnomad AFR AF: 0.0672

Gnomad AMI AF: 0.0257

Gnomad AMR AF: 0.0597

Gnomad ASJ AF: 0.0657

Gnomad EAS AF: 0.0264

Gnomad SAS AF: 0.0459

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.0662

Gnomad NFE AF: 0.0901

Gnomad OTH AF: 0.0850

GnomAD4 exome AF: 0.157 AC: 157 AN: 1000 Hom.: 3 Cov.: 0 AF XY: 0.138 AC XY: 72 AN XY: 522

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

African (AFR) AF: 0.150 AC: 3 AN: 20

American (AMR) AF: 0.0833 AC: 3 AN: 36

Ashkenazi Jewish (ASJ) AF: 0.0875 AC: 7 AN: 80

East Asian (EAS) AF: 0.154 AC: 28 AN: 182

South Asian (SAS) AF: 0.100 AC: 2 AN: 20

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

Middle Eastern (MID) AF: 0.250 AC: 1 AN: 4

European-Non Finnish (NFE) AF: 0.185 AC: 106 AN: 572

Other (OTH) AF: 0.0854 AC: 7 AN: 82

⚠️ 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: 0.0792 AC: 11490 AN: 145080 Hom.: 469 Cov.: 24 AF XY: 0.0784 AC XY: 5529 AN XY: 70524

African (AFR) AF: 0.0674 AC: 2679 AN: 39740

American (AMR) AF: 0.0596 AC: 874 AN: 14656

Ashkenazi Jewish (ASJ) AF: 0.0657 AC: 221 AN: 3366

East Asian (EAS) AF: 0.0265 AC: 132 AN: 4986

South Asian (SAS) AF: 0.0462 AC: 209 AN: 4520

European-Finnish (FIN) AF: 0.138 AC: 1247 AN: 9020

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

European-Non Finnish (NFE) AF: 0.0902 AC: 5920 AN: 65656

Other (OTH) AF: 0.0845 AC: 166 AN: 1964

Alfa AF: 0.0377 Hom.: 32

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Hypoparathyroidism, deafness, renal disease syndrome (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; COSMIC: COSV60516175; COSMIC: COSV60516175;