rs372548249

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_006195.6(PBX3):​c.236C>A​(p.Ala79Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A79G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

PBX3
NM_006195.6 missense

Scores

8
8
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.57
Variant links:
Genes affected
PBX3 (HGNC:8634): (PBX homeobox 3) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in animal organ development; neuron development; and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within several processes, including adult locomotory behavior; dorsal spinal cord development; and regulation of respiratory gaseous exchange by nervous system process. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

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, 0.887

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PBX3NM_006195.6 linkc.236C>A p.Ala79Glu missense_variant Exon 2 of 9 ENST00000373489.10 NP_006186.1 P40426-1Q96AL5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PBX3ENST00000373489.10 linkc.236C>A p.Ala79Glu missense_variant Exon 2 of 9 1 NM_006195.6 ENSP00000362588.5 P40426-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
1.0
BayesDel_addAF
Pathogenic
0.30
D
BayesDel_noAF
Pathogenic
0.19
CADD
Pathogenic
31
DANN
Uncertain
0.99
DEOGEN2
Benign
0.24
.;T;T;.;.
Eigen
Pathogenic
0.84
Eigen_PC
Pathogenic
0.78
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Pathogenic
0.99
D;D;D;D;D
M_CAP
Benign
0.083
D
MetaRNN
Pathogenic
0.89
D;D;D;D;D
MetaSVM
Uncertain
-0.27
T
MutationAssessor
Uncertain
2.6
M;.;M;.;.
PrimateAI
Pathogenic
0.91
D
PROVEAN
Uncertain
-3.7
D;D;D;.;D
REVEL
Uncertain
0.51
Sift
Uncertain
0.0010
D;D;D;.;D
Sift4G
Uncertain
0.0020
D;D;D;D;D
Polyphen
0.99
.;.;D;.;.
Vest4
0.94
MutPred
0.78
Gain of loop (P = 0.0166);Gain of loop (P = 0.0166);Gain of loop (P = 0.0166);.;.;
MVP
0.80
MPC
1.0
ClinPred
1.0
D
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.1
Varity_R
0.91
gMVP
0.88

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs372548249; hg19: chr9-128510864; API