chr9-125957570-G-A

Variant names:

• chr9-125957570-G-A
• rs10513456
• NM_006195.6:c.844-3114G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006195.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PBX3	NM_006195.6	MANE Select	c.844-3114G>A		intron	N/A	NP_006186.1	P40426-1
	PBX3	NM_001411009.1		c.907-3114G>A		intron	N/A	NP_001397938.1	Q5JS98
	PBX3	NM_001134778.2		c.619-3114G>A		intron	N/A	NP_001128250.1	P40426-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PBX3	ENST00000373489.10	TSL:1 MANE Select	c.844-3114G>A		intron	N/A	ENSP00000362588.5	P40426-1
	PBX3	ENST00000447726.6	TSL:1	c.619-3114G>A		intron	N/A	ENSP00000387456.2	P40426-5
	PBX3	ENST00000373482.6	TSL:1	n.*320-3114G>A		intron	N/A	ENSP00000362581.2	H3BLX0

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

African (AFR) AF: 0.417 AC: 17291 AN: 41454

American (AMR) AF: 0.707 AC: 10804 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.650 AC: 2255 AN: 3470

East Asian (EAS) AF: 0.767 AC: 3974 AN: 5178

South Asian (SAS) AF: 0.725 AC: 3498 AN: 4824

European-Finnish (FIN) AF: 0.828 AC: 8757 AN: 10582

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.684 AC: 46485 AN: 67976

Other (OTH) AF: 0.652 AC: 1376 AN: 2110

Alfa AF: 0.656 Hom.: 84542

Bravo AF: 0.609

Asia WGS AF: 0.724 AC: 2519 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	6.8
DANN	Benign	0.48
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10513456; hg19: chr9-128719849;