Variant 9-125747619-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006195.6(PBX3):c.166A>G(p.Ile56Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000345 in 1,447,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

PBX3
NM_006195.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.19

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]

PBX3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36691815).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PBX3	NM_006195.6 linkuse as main transcript	c.166A>G	p.Ile56Val	missense_variant	1/9	ENST00000373489.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PBX3	ENST00000373489.10 linkuse as main transcript	c.166A>G	p.Ile56Val	missense_variant	1/9	1	NM_006195.6	A1	P40426-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000430

AC:

AN:

232362

Hom.:

AF XY:

0.00000788

AC XY:

AN XY:

126838

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000956

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000345

AC:

AN:

1447656

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

720314

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000362

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

Alfa

AF:

0.000111

Hom.:

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

Jun 05, 2023

The c.166A>G (p.I56V) alteration is located in exon 1 (coding exon 1) of the PBX3 gene. This alteration results from a A to G substitution at nucleotide position 166, causing the isoleucine (I) at amino acid position 56 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.77

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

Cadd

Pathogenic

Dann

Uncertain

0.99

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.87

D;D;D

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.37

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.3

M;.;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.64

N;N;N

REVEL

Benign

0.14

Sift

Benign

0.038

D;D;D

Sift4G

Benign

0.066

T;D;T

Polyphen

0.88

.;.;P

Vest4

0.49

MutPred

0.67

Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);

MVP

0.25

MPC

0.41

ClinPred

0.55

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over