10-8069658-C-T

Variant names:

• chr10-8069658-C-T
• rs406103
• NM_001002295.2:c.1050+60C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001002295.2(GATA3):​c.1050+60C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 1,588,650 control chromosomes in the GnomAD database, including 42,160 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5626 hom., cov: 31)
  • Exomes 𝑓: 0.22 (36534 hom.)
• Consequence: GATA3 NM_001002295.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.94
• Publications: 15 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 Gene-Disease associations (from GenCC):

• hypoparathyroidism-deafness-renal disease syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 10-8069658-C-T is Benign according to our data. Variant chr10-8069658-C-T is described in ClinVar as Benign. ClinVar VariationId is 682790.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.372 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.1050+60C>T		intron	N/A	NP_001002295.1
	GATA3	NM_001441115.1		c.1050+60C>T		intron	N/A	NP_001428044.1
	GATA3	NM_001441116.1		c.1050+60C>T		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.1050+60C>T		intron	N/A	ENSP00000368632.3
	GATA3	ENST00000346208.4	TSL:1	c.1047+60C>T		intron	N/A	ENSP00000341619.3
	GATA3	ENST00000872595.1		c.1050+60C>T		intron	N/A	ENSP00000542654.1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39670 AN: 151884 Hom.: 5615 Cov.: 31

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.241

GnomAD4 exome AF: 0.222 AC: 319093 AN: 1436648 Hom.: 36534 AF XY: 0.225 AC XY: 160489 AN XY: 714752

African (AFR) AF: 0.393 AC: 12967 AN: 33028

American (AMR) AF: 0.141 AC: 6036 AN: 42960

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 7642 AN: 25838

East Asian (EAS) AF: 0.277 AC: 10891 AN: 39306

South Asian (SAS) AF: 0.271 AC: 23092 AN: 85122

European-Finnish (FIN) AF: 0.250 AC: 13216 AN: 52770

Middle Eastern (MID) AF: 0.299 AC: 1707 AN: 5718

European-Non Finnish (NFE) AF: 0.210 AC: 229282 AN: 1092332

Other (OTH) AF: 0.239 AC: 14260 AN: 59574

GnomAD4 genome AF: 0.261 AC: 39708 AN: 152002 Hom.: 5626 Cov.: 31 AF XY: 0.261 AC XY: 19411 AN XY: 74304

African (AFR) AF: 0.377 AC: 15621 AN: 41418

American (AMR) AF: 0.166 AC: 2541 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1034 AN: 3470

East Asian (EAS) AF: 0.265 AC: 1368 AN: 5168

South Asian (SAS) AF: 0.265 AC: 1280 AN: 4828

European-Finnish (FIN) AF: 0.254 AC: 2690 AN: 10576

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14349 AN: 67936

Other (OTH) AF: 0.237 AC: 499 AN: 2108

Alfa AF: 0.241 Hom.: 786

Bravo AF: 0.261

Asia WGS AF: 0.237 AC: 823 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.077
DANN	Benign	0.78
PhyloP100		-2.9
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: rs406103; hg19: chr10-8111621; COSMIC: COSV60517839;