rs10513456

Positions:

• chr9-125957570-G-A
• chr9-125957570-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006195.6(PBX3):​c.844-3114G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 152,090 control chromosomes in the GnomAD database, including 31,407 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.63 (31407 hom., cov: 32)
• Consequence: PBX3 NM_006195.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.234

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PBX3	NM_006195.6	c.844-3114G>A		intron_variant		ENST00000373489.10	NP_006186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PBX3	ENST00000373489.10	c.844-3114G>A		intron_variant		1	NM_006195.6	ENSP00000362588	A1

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95356 AN: 151972 Hom.: 31399 Cov.: 32

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.706

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.767

Gnomad SAS AF: 0.727

Gnomad FIN AF: 0.828

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.648

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.627 AC: 95391 AN: 152090 Hom.: 31407 Cov.: 32 AF XY: 0.638 AC XY: 47430 AN XY: 74348

Gnomad4 AFR AF: 0.417

Gnomad4 AMR AF: 0.707

Gnomad4 ASJ AF: 0.650

Gnomad4 EAS AF: 0.767

Gnomad4 SAS AF: 0.725

Gnomad4 FIN AF: 0.828

Gnomad4 NFE AF: 0.684

Gnomad4 OTH AF: 0.652

Alfa AF: 0.674 Hom.: 56229

Bravo AF: 0.609

Asia WGS AF: 0.724 AC: 2519 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	6.8
DANN	Benign	0.48

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

Other links and lift over

dbSNP: rs10513456; hg19: chr9-128719849;