NM_001002295.2:c.778+1123T>C

Variant names:

• chr10-8059964-T-C
• rs3781093
• NM_001002295.2:c.778+1123T>C

GermlineCancer (beta)

Variant summary

Our verdict is Benign.

<-10 Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -14 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_StrongBP6_Moderate

The NM_001002295.2(GATA3):c.778+1123T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.193 (AC=29,396) in the gnomAD database across 152,096 control chromosomes, including 3,087 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.292. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign/Likely Benign (★).

• Frequency: Genomes: 𝑓 0.19 (3087 hom., cov: 33)
• Consequence: GATA3 NM_001002295.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.464
• Publications: 29 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, PanelApp Australia, Orphanet, G2P, Labcorp Genetics (formerly Invitae)

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Benign. The variant received -14 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).
	BP6Reputable source reports benign		ClinVar 1-star benign — moderate (BP6); ClinVar germline classification: Benign/Likely Benign, 1 star(s).
	BA1Stand-alone benign allele frequency (>5%)		GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.2922 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_001002295.2. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	GATA3 NM_001002295.2	MANE Select	c.778+1123T>C	intron	Intron 3 of 5	Prot: NP_001002295.1 UniProt:
	GATA3 NM_001441115.1		c.778+1123T>C	intron	Intron 3 of 5	Prot: NP_001428044.1 UniProt:
	GATA3 NM_001441116.1		c.778+1123T>C	intron	Intron 4 of 6	Prot: NP_001428045.1 UniProt:

GATA3 NM_001002295.2

MANE Select

HGVSc / HGVSpc.778+1123T>C

Exon rankIntron 3 of 5

intron

Prot: NP_001002295.1UniProt: P23771-2

GATA3 NM_001441115.1

HGVSc / HGVSpc.778+1123T>C

Exon rankIntron 3 of 5

intron

Prot: NP_001428044.1UniProt: P23771-2

GATA3 NM_001441116.1

HGVSc / HGVSpc.778+1123T>C

Exon rankIntron 4 of 6

intron

Prot: NP_001428045.1UniProt: P23771-2

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	GATA3 ENST00000379328.9	TSL:1MANE Select	c.778+1123T>C	intron	Intron 3 of 5	Prot: ENSP00000368632.3 UniProt:
	GATA3 ENST00000346208.4	TSL:1	c.778+1123T>C	intron	Intron 3 of 5	Prot: ENSP00000341619.3 UniProt:
	GATA3 ENST00000872595.1		c.778+1123T>C	intron	Intron 4 of 6	Prot: ENSP00000542654.1 UniProt:

GATA3 ENST00000379328.9

TSL:1MANE Select

HGVSc / HGVSpc.778+1123T>C

Exon rankIntron 3 of 5

intron

Prot: ENSP00000368632.3UniProt: P23771-2

GATA3 ENST00000346208.4

TSL:1

HGVSc / HGVSpc.778+1123T>C

Exon rankIntron 3 of 5

intron

Prot: ENSP00000341619.3UniProt: P23771-1

GATA3 ENST00000872595.1

HGVSc / HGVSpc.778+1123T>C

Exon rankIntron 4 of 6

intron

Prot: ENSP00000542654.1UniProt: P23771-2

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 4 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.193	AC:29376	Hom:3080	AN:151978	Cov:33
GnomAD4 genome	AF: 0.193	AC:29396	Hom:3087	AN:152096	Cov:33
TOPMed (Bravo)	AF: 0.206	AC:54567	Hom:6384	AN:264690	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.176	AC:27177	Hom:2636	AN:153994	Cov:
Local & regional cohorts 10 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.221	AC:518	Hom:59	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.329	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.173	AC:52	Hom:	AN:300	Cov:
GenomeAsia100K	AF: 0.213	AC:740	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.316	AC:2284	Hom:	AN:7232	Cov:
Qatari Genome	AF: 0.239	AC:42	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.289	AC:35421	Hom:5140	AN:122610	Cov:
Turkish Variome	AF: 0.273	AC:422	Hom:49	AN:1546	Cov:
UK10K	AF: 0.138	AC:1046	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.309	AC:2768	Hom:429	AN:8960	Cov:

Showing 14 sources

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	B-cell childhood acute lymphoblastic leukemia (1)

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	0.66
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.2
DANN	Benign	0.48
GPN-Star LLR	N/A	0.022
GPN-Star score	N/A	-0.022
Mutation Taster	N/A	100/0	polymorphism (auto)
PhyloP100	Benign	-0.46

Showing 8 of 8 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs3781093;

hg19: chr10-8101927;

COSMIC: COSV60522152;

COSMIC: COSV60522152;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar