10-8069446-C-T

Variant names:

• chr10-8069446-C-T
• rs422628
• NM_001002295.2:c.925-27C>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.925-27C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.774 in 1,606,638 control chromosomes in the GnomAD database, including 483,999 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.77 (45354 hom., cov: 26)
  • Exomes 𝑓: 0.77 (438645 hom.)
• Consequence: GATA3 NM_001002295.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.69
• Publications: 19 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: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 3 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 10-8069446-C-T is Benign according to our data. Variant chr10-8069446-C-T is described in ClinVar as Benign. ClinVar VariationId is 1234255.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.934 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.925-27C>T		intron	N/A	NP_001002295.1
	GATA3	NM_001441115.1		c.925-27C>T		intron	N/A	NP_001428044.1
	GATA3	NM_001441116.1		c.925-27C>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.925-27C>T		intron	N/A	ENSP00000368632.3
	GATA3	ENST00000346208.4	TSL:1	c.922-27C>T		intron	N/A	ENSP00000341619.3
	GATA3	ENST00000872595.1		c.925-27C>T		intron	N/A	ENSP00000542654.1

Frequencies

GnomAD3 genomes AF: 0.774 AC: 116869 AN: 150936 Hom.: 45328 Cov.: 26

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.876

Gnomad AMR AF: 0.831

Gnomad ASJ AF: 0.841

Gnomad EAS AF: 0.956

Gnomad SAS AF: 0.847

Gnomad FIN AF: 0.797

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.759

Gnomad OTH AF: 0.791

GnomAD2 exomes AF: 0.806 AC: 202332 AN: 251036 AF XY: 0.806

Gnomad AFR exome AF: 0.733

Gnomad AMR exome AF: 0.876

Gnomad ASJ exome AF: 0.836

Gnomad EAS exome AF: 0.953

Gnomad FIN exome AF: 0.798

Gnomad NFE exome AF: 0.764

Gnomad OTH exome AF: 0.795

GnomAD4 exome AF: 0.774 AC: 1127126 AN: 1455586 Hom.: 438645 Cov.: 34 AF XY: 0.777 AC XY: 562880 AN XY: 724524

African (AFR) AF: 0.733 AC: 24432 AN: 33330

American (AMR) AF: 0.872 AC: 38978 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.834 AC: 21771 AN: 26114

East Asian (EAS) AF: 0.957 AC: 37988 AN: 39684

South Asian (SAS) AF: 0.833 AC: 71778 AN: 86144

European-Finnish (FIN) AF: 0.797 AC: 42444 AN: 53274

Middle Eastern (MID) AF: 0.798 AC: 4598 AN: 5762

European-Non Finnish (NFE) AF: 0.757 AC: 837654 AN: 1106376

Other (OTH) AF: 0.789 AC: 47483 AN: 60190

GnomAD4 genome AF: 0.774 AC: 116943 AN: 151052 Hom.: 45354 Cov.: 26 AF XY: 0.778 AC XY: 57400 AN XY: 73732

African (AFR) AF: 0.732 AC: 30032 AN: 41002

American (AMR) AF: 0.831 AC: 12631 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.841 AC: 2912 AN: 3462

East Asian (EAS) AF: 0.956 AC: 4927 AN: 5152

South Asian (SAS) AF: 0.847 AC: 4025 AN: 4754

European-Finnish (FIN) AF: 0.797 AC: 8282 AN: 10396

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.759 AC: 51450 AN: 67810

Other (OTH) AF: 0.794 AC: 1649 AN: 2078

Alfa AF: 0.770 Hom.: 54005

Bravo AF: 0.776

Asia WGS AF: 0.875 AC: 3041 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Hypoparathyroidism, deafness, renal disease syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.091
DANN	Benign	0.56
PhyloP100		-1.7
BranchPoint Hunter		3.0
Mutation Taster		=11/89	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs422628; hg19: chr10-8111409;