rs28936696
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3PP5
The NM_001321120.2(TBX4):c.1595A>G(p.Gln532Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
TBX4
NM_001321120.2 missense
NM_001321120.2 missense
Scores
5
9
5
Clinical Significance
Conservation
PhyloP100: 4.44
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 Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.782
PP5
Variant 17-61483470-A-G is Pathogenic according to our data. Variant chr17-61483470-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 7857.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TBX4 | NM_001321120.2 | c.1595A>G | p.Gln532Arg | missense_variant | 9/9 | ENST00000644296.1 | NP_001308049.1 | |
TBX4 | NM_018488.3 | c.1592A>G | p.Gln531Arg | missense_variant | 8/8 | NP_060958.2 | ||
TBX4 | XM_011525490.3 | c.1784A>G | p.Gln595Arg | missense_variant | 9/9 | XP_011523792.1 | ||
TBX4 | XM_011525491.3 | c.1781A>G | p.Gln594Arg | missense_variant | 9/9 | XP_011523793.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TBX4 | ENST00000644296.1 | c.1595A>G | p.Gln532Arg | missense_variant | 9/9 | NM_001321120.2 | ENSP00000495986.1 | |||
TBX4 | ENST00000240335.1 | c.1592A>G | p.Gln531Arg | missense_variant | 8/8 | 1 | ENSP00000240335.1 | |||
TBX4 | ENST00000642491.1 | c.1595A>G | p.Gln532Arg | missense_variant | 8/8 | ENSP00000495714.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 35
GnomAD4 exome
Cov.:
35
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Coxopodopatellar syndrome Pathogenic:1Other:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 01, 2004 | - - |
not provided, no classification provided | literature only | Wendy Chung Laboratory, Columbia University Medical Center | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;.;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
.;.;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
.;.;M;.
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;N;.
REVEL
Pathogenic
Sift
Uncertain
D;.;D;.
Sift4G
Pathogenic
D;.;D;.
Polyphen
0.60
.;.;P;.
Vest4
MutPred
0.74
.;.;Gain of catalytic residue at Q531 (P = 0.0352);.;
MVP
MPC
0.69
ClinPred
D
GERP RS
Varity_R
gMVP
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