chr19-19599328-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_025245.3(PBX4):c.157C>G(p.Leu53Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000347 in 1,613,388 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000036 ( 0 hom. )
Consequence
PBX4
NM_025245.3 missense
NM_025245.3 missense
Scores
1
6
12
Clinical Significance
Conservation
PhyloP100: 5.83
Genes affected
PBX4 (HGNC:13403): (PBX homeobox 4) This gene encodes a member of the pre-B cell leukemia transcription factor family. These proteins are homeobox proteins that play critical roles in embryonic development and cellular differentiation both as Hox cofactors and through Hox-independent pathways. The encoded protein contains a homeobox DNA-binding domain, but specific functions of the protein have not been determined. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, May 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.745
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PBX4 | NM_025245.3 | c.157C>G | p.Leu53Val | missense_variant | 2/8 | ENST00000251203.14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PBX4 | ENST00000251203.14 | c.157C>G | p.Leu53Val | missense_variant | 2/8 | 1 | NM_025245.3 | P1 | |
PBX4 | ENST00000557978.6 | c.157C>G | p.Leu53Val | missense_variant, NMD_transcript_variant | 2/8 | 1 | |||
PBX4 | ENST00000558222.1 | c.157C>G | p.Leu53Val | missense_variant, NMD_transcript_variant | 2/6 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152156Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251392Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135868
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GnomAD4 exome AF: 0.0000356 AC: 52AN: 1461232Hom.: 0 Cov.: 30 AF XY: 0.0000399 AC XY: 29AN XY: 726916
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152156Hom.: 0 Cov.: 31 AF XY: 0.0000538 AC XY: 4AN XY: 74332
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 30, 2021 | The c.157C>G (p.L53V) alteration is located in exon 2 (coding exon 2) of the PBX4 gene. This alteration results from a C to G substitution at nucleotide position 157, causing the leucine (L) at amino acid position 53 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N
REVEL
Benign
Sift
Benign
D
Sift4G
Benign
T
Polyphen
P
Vest4
MutPred
Gain of catalytic residue at L53 (P = 0.0988);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at