rs1554488651
Variant summary
Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP3
The NM_001308093.3(GATA4):c.525_530dupAGCCGC(p.Ala176_Ala177dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A177A) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 7.4e-7 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
GATA4
NM_001308093.3 disruptive_inframe_insertion
NM_001308093.3 disruptive_inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.21
Publications
0 publications found
Genes affected
GATA4 (HGNC:4173): (GATA binding protein 4) This gene encodes a member of the GATA family of zinc-finger transcription factors. Members of this family recognize the GATA motif which is present in the promoters of many genes. This protein is thought to regulate genes involved in embryogenesis and in myocardial differentiation and function, and is necessary for normal testicular development. Mutations in this gene have been associated with cardiac septal defects. Additionally, alterations in gene expression have been associated with several cancer types. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]
GATA4 Gene-Disease associations (from GenCC):
- atrial septal defect 2Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
- structural congenital heart disease, multiple types - GATA4Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- testicular anomalies with or without congenital heart diseaseInheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
- metabolic syndromeInheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
- neonatal diabetes mellitusInheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
- pancreatic hypoplasia-diabetes-congenital heart disease syndromeInheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
- permanent neonatal diabetes mellitusInheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
- transient neonatal diabetes mellitusInheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
- 46,XY partial gonadal dysgenesisInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- familial atrial fibrillationInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- tetralogy of fallotInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- dilated cardiomyopathyInheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP3
Nonframeshift variant in repetitive region in NM_001308093.3
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001308093.3. 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 |
|---|---|---|---|---|---|---|---|---|---|
| GATA4 | NM_001308093.3 | MANE Select | c.525_530dupAGCCGC | p.Ala176_Ala177dup | disruptive_inframe_insertion | Exon 2 of 7 | NP_001295022.1 | P43694-2 | |
| GATA4 | NM_002052.5 | c.525_530dupAGCCGC | p.Ala176_Ala177dup | disruptive_inframe_insertion | Exon 2 of 7 | NP_002043.2 | |||
| GATA4 | NM_001308094.2 | c.-6+8059_-6+8064dupAGCCGC | intron | N/A | NP_001295023.1 | B3KUF4 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| GATA4 | ENST00000532059.6 | TSL:1 MANE Select | c.525_530dupAGCCGC | p.Ala176_Ala177dup | disruptive_inframe_insertion | Exon 2 of 7 | ENSP00000435712.1 | P43694-2 | |
| GATA4 | ENST00000886854.1 | c.525_530dupAGCCGC | p.Ala176_Ala177dup | disruptive_inframe_insertion | Exon 2 of 7 | ENSP00000556913.1 | |||
| GATA4 | ENST00000886846.1 | c.525_530dupAGCCGC | p.Ala176_Ala177dup | disruptive_inframe_insertion | Exon 3 of 8 | ENSP00000556905.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.44e-7 AC: 1AN: 1343260Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 662676 show subpopulations
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
1
AN:
1343260
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
662676
show subpopulations
African (AFR)
AF:
AC:
0
AN:
27100
American (AMR)
AF:
AC:
0
AN:
31178
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
23458
East Asian (EAS)
AF:
AC:
0
AN:
31200
South Asian (SAS)
AF:
AC:
0
AN:
75192
European-Finnish (FIN)
AF:
AC:
0
AN:
33180
Middle Eastern (MID)
AF:
AC:
0
AN:
3962
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1062158
Other (OTH)
AF:
AC:
0
AN:
55832
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
Atrioventricular septal defect 4 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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