chr10-8073874-G-T

Variant names:

• chr10-8073874-G-T
• rs200935603
• NM_001002295.2:c.1186G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001002295.2(GATA3):​c.1186G>T​(p.Ala396Ser) variant causes a missense change. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A396T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GATA3 NM_001002295.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.82
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21699625).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA3	NM_001002295.2	MANE Select	c.1186G>T	p.Ala396Ser	missense	Exon 6 of 6	NP_001002295.1
	GATA3	NM_001441115.1		c.1186G>T	p.Ala396Ser	missense	Exon 6 of 6	NP_001428044.1
	GATA3	NM_001441116.1		c.1186G>T	p.Ala396Ser	missense	Exon 7 of 7	NP_001428045.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATA3	ENST00000379328.9	TSL:1 MANE Select	c.1186G>T	p.Ala396Ser	missense	Exon 6 of 6	ENSP00000368632.3
	GATA3	ENST00000346208.4	TSL:1	c.1183G>T	p.Ala395Ser	missense	Exon 6 of 6	ENSP00000341619.3
	GATA3	ENST00000461472.1	TSL:3	c.*131G>T		3_prime_UTR	Exon 3 of 3	ENSP00000515407.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Uncertain	0.065	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	23
DANN	Benign	0.97
DEOGEN2	Uncertain	0.43	T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.22	T
MetaSVM	Pathogenic	0.79	D
MutationAssessor	Benign	0.95	L
PhyloP100		5.8
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.43	N
REVEL	Uncertain	0.47
Sift	Benign	0.31	T
Sift4G	Benign	0.25	T
Polyphen		0.0060	B
Vest4		0.084
MutPred		0.29		Gain of phosphorylation at A395 (P = 0.0211)
MVP		0.76
MPC		1.1
ClinPred		0.87	D
GERP RS		5.3
Varity_R		0.16
gMVP		0.83
Mutation Taster		=72/28	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs200935603; hg19: chr10-8115837;