Genetic Variant NM_001002295.2:c.778+1123T>C (chr10-8059964-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is 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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.464

Publications

29 publications found

Variant links:

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)

GATA3 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001002295.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

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

Show applied only (3)

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

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: P23771-2
GATA3 NM_001441115.1		c.778+1123T>C	intron	Intron 3 of 5	Prot: NP_001428044.1 UniProt: P23771-2
GATA3 NM_001441116.1		c.778+1123T>C	intron	Intron 4 of 6	Prot: NP_001428045.1 UniProt: P23771-2

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

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: P23771-2
GATA3 ENST00000346208.4	TSL:1	c.778+1123T>C	intron	Intron 3 of 5	Prot: ENSP00000341619.3 UniProt: P23771-1
GATA3 ENST00000872595.1		c.778+1123T>C	intron	Intron 4 of 6	Prot: ENSP00000542654.1 UniProt: P23771-2

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

View on ClinVar

Pathogenic

VUS

Benign

Condition

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.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational Scores

Splicing Scores

MaveDB functional evidence ?

Publications

Other links and lift over

MaveDB functional evidence