9-125846216-G-T

Variant names:

• chr9-125846216-G-T
• rs10760403
• NM_006195.6:c.275-69470G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006195.6(PBX3):​c.275-69470G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 151,842 control chromosomes in the GnomAD database, including 38,589 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 0.71 (38589 hom., cov: 31)
• Consequence: PBX3 NM_006195.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.326
• Publications: 2 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]

LOC124902271 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PBX3	NM_006195.6	c.275-69470G>T		intron_variant	Intron 2 of 8	ENST00000373489.10	NP_006186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PBX3	ENST00000373489.10	c.275-69470G>T		intron_variant	Intron 2 of 8	1	NM_006195.6	ENSP00000362588.5

Frequencies

GnomAD3 genomes AF: 0.708 AC: 107356 AN: 151724 Hom.: 38546 Cov.: 31

Gnomad AFR AF: 0.804

Gnomad AMI AF: 0.793

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.761

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.790

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.636

Gnomad OTH AF: 0.705

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

GnomAD4 genome AF: 0.708 AC: 107461 AN: 151842 Hom.: 38589 Cov.: 31 AF XY: 0.714 AC XY: 52997 AN XY: 74210

African (AFR) AF: 0.804 AC: 33302 AN: 41410

American (AMR) AF: 0.719 AC: 10946 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 1963 AN: 3466

East Asian (EAS) AF: 0.762 AC: 3928 AN: 5158

South Asian (SAS) AF: 0.705 AC: 3397 AN: 4820

European-Finnish (FIN) AF: 0.790 AC: 8351 AN: 10566

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.636 AC: 43153 AN: 67882

Other (OTH) AF: 0.709 AC: 1497 AN: 2112

Alfa AF: 0.620 Hom.: 2199

Bravo AF: 0.707

Asia WGS AF: 0.738 AC: 2551 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.074
DANN	Benign	0.47
PhyloP100		-0.33
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: rs10760403; hg19: chr9-128608495;