NM_006195.6:c.797A>C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_006195.6(PBX3):​c.797A>C​(p.Glu266Ala) 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. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

PBX3
NM_006195.6 missense

Scores

9
6
4

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 8.95
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]

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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, 0.817

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PBX3NM_006195.6 linkc.797A>C p.Glu266Ala missense_variant Exon 5 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.797A>C p.Glu266Ala missense_variant Exon 5 of 9 1 NM_006195.6 ENSP00000362588.5 P40426-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

X-linked cone-rod dystrophy Uncertain:1
Jan 03, 2023
Genetic Eye Disease Investigation Unit, University of Auckland
Significance: Uncertain significance
Review Status: no assertion criteria provided
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.98
BayesDel_addAF
Pathogenic
0.36
D
BayesDel_noAF
Pathogenic
0.27
CADD
Pathogenic
31
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.69
.;D;D;.
Eigen
Uncertain
0.51
Eigen_PC
Uncertain
0.59
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.95
D;D;D;D
M_CAP
Uncertain
0.26
D
MetaRNN
Pathogenic
0.82
D;D;D;D
MetaSVM
Pathogenic
0.91
D
MutationAssessor
Benign
0.82
L;.;L;.
PrimateAI
Pathogenic
0.83
D
PROVEAN
Pathogenic
-5.5
D;D;D;D
REVEL
Pathogenic
0.81
Sift
Benign
0.073
T;D;D;T
Sift4G
Benign
0.092
T;D;T;T
Polyphen
1.0, 0.94
.;D;P;.
Vest4
0.78
MutPred
0.54
Gain of methylation at K268 (P = 0.1247);Gain of methylation at K268 (P = 0.1247);Gain of methylation at K268 (P = 0.1247);.;
MVP
0.89
MPC
2.8
ClinPred
0.99
D
GERP RS
5.4
Varity_R
0.58
gMVP
0.83

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-128697840; API