10-8058636-C-A

Variant names:

• chr10-8058636-C-A
• rs35508267
• NM_001002295.2:c.573C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001002295.2(GATA3):​c.573C>A​(p.Pro191Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P191P) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GATA3 NM_001002295.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19
• 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 Gene-Disease associations (from GenCC):

• hypoparathyroidism-deafness-renal disease syndrome

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

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP7: Synonymous conserved (PhyloP=-1.19 with no splicing effect.

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.573C>A	p.Pro191Pro	synonymous	Exon 3 of 6	NP_001002295.1	P23771-2
	GATA3	NM_001441115.1		c.573C>A	p.Pro191Pro	synonymous	Exon 3 of 6	NP_001428044.1
	GATA3	NM_001441116.1		c.573C>A	p.Pro191Pro	synonymous	Exon 4 of 7	NP_001428045.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA3	ENST00000379328.9	TSL:1 MANE Select	c.573C>A	p.Pro191Pro	synonymous	Exon 3 of 6	ENSP00000368632.3	P23771-2
	GATA3	ENST00000346208.4	TSL:1	c.573C>A	p.Pro191Pro	synonymous	Exon 3 of 6	ENSP00000341619.3	P23771-1
	GATA3	ENST00000872595.1		c.573C>A	p.Pro191Pro	synonymous	Exon 4 of 7	ENSP00000542654.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	3.0
DANN	Benign	0.88
PhyloP100		-1.2

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: rs35508267; hg19: chr10-8100599;