chr9-125747475-C-G
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_006195.6(PBX3):c.22C>G(p.Leu8Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000099 in 1,576,150 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00042 ( 0 hom., cov: 29)
Exomes 𝑓: 0.000065 ( 0 hom. )
Consequence
PBX3
NM_006195.6 missense
NM_006195.6 missense
Scores
2
4
12
Clinical Significance
Conservation
PhyloP100: 0.289
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 Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.029993981).
BS2
?
High AC in GnomAd at 63 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PBX3 | NM_006195.6 | c.22C>G | p.Leu8Val | missense_variant | 1/9 | ENST00000373489.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PBX3 | ENST00000373489.10 | c.22C>G | p.Leu8Val | missense_variant | 1/9 | 1 | NM_006195.6 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000418 AC: 63AN: 150618Hom.: 0 Cov.: 29
GnomAD3 genomes
?
AF:
AC:
63
AN:
150618
Hom.:
Cov.:
29
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000153 AC: 31AN: 202416Hom.: 0 AF XY: 0.000125 AC XY: 14AN XY: 111668
GnomAD3 exomes
AF:
AC:
31
AN:
202416
Hom.:
AF XY:
AC XY:
14
AN XY:
111668
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000652 AC: 93AN: 1425532Hom.: 0 Cov.: 32 AF XY: 0.0000579 AC XY: 41AN XY: 708620
GnomAD4 exome
AF:
AC:
93
AN:
1425532
Hom.:
Cov.:
32
AF XY:
AC XY:
41
AN XY:
708620
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 ? AF: 0.000418 AC: 63AN: 150618Hom.: 0 Cov.: 29 AF XY: 0.000394 AC XY: 29AN XY: 73542
GnomAD4 genome
?
AF:
AC:
63
AN:
150618
Hom.:
Cov.:
29
AF XY:
AC XY:
29
AN XY:
73542
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
6
ESP6500EA
AF:
AC:
0
ExAC
?
AF:
AC:
16
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 | Feb 12, 2024 | The c.22C>G (p.L8V) alteration is located in exon 1 (coding exon 1) of the PBX3 gene. This alteration results from a C to G substitution at nucleotide position 22, causing the leucine (L) at amino acid position 8 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
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D;D
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;N
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;T
Polyphen
0.0020
.;.;B
Vest4
MVP
MPC
0.41
ClinPred
T
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