chr17-61456633-CG-C
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001321120.2(TBX4):c.146del(p.Gly49AspfsTer39) variant causes a frameshift 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 Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
TBX4
NM_001321120.2 frameshift
NM_001321120.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.167
Genes affected
TBX4 (HGNC:11603): (T-box transcription factor 4) This gene is a member of a phylogenetically conserved family of genes that share a common DNA-binding domain, the T-box. T-box genes encode transcription factors involved in the regulation of developmental processes. This gene is the human homolog of mouse Tbx4, which is closely linked to Tbx2 on mouse chromosome 11. Similarly this gene, like TBX2, maps to human chromosome 17. Expression studies in mouse and chicken show that Tbx4 is expressed in developing hindlimb, but not in forelimb buds, suggesting a role for this gene in regulating limb development and specification of limb identity. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 17-61456633-CG-C is Pathogenic according to our data. Variant chr17-61456633-CG-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1341436.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TBX4 | NM_001321120.2 | c.146del | p.Gly49AspfsTer39 | frameshift_variant | 2/9 | ENST00000644296.1 | |
LOC124904042 | XR_007065872.1 | n.2069del | non_coding_transcript_exon_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBX4 | ENST00000644296.1 | c.146del | p.Gly49AspfsTer39 | frameshift_variant | 2/9 | NM_001321120.2 | A1 | ||
TBX4 | ENST00000240335.1 | c.146del | p.Gly49AspfsTer39 | frameshift_variant | 1/8 | 1 | P4 | ||
TBX4 | ENST00000642491.1 | c.146del | p.Gly49AspfsTer39 | frameshift_variant | 1/8 | A1 | |||
TBX4 | ENST00000589003.5 | c.-113del | 5_prime_UTR_variant | 2/6 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1208812Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 588902
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1208812
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
588902
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Pulmonary hypertension, primary, 1 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | literature only;research | Wendy Chung Laboratory, Columbia University Medical Center | Nov 01, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.