NM_006195.6:c.274+18076T>A

Variant names:

• chr9-125766699-T-A
• rs7040561
• NM_006195.6:c.274+18076T>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_006195.6(PBX3):​c.274+18076T>A variant causes a intron change. The variant allele was found at a frequency of 0.901 in 152,200 control chromosomes in the GnomAD database, including 61,962 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 0.90 (61962 hom., cov: 32)
• Consequence: PBX3 NM_006195.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.71
• Publications: 8 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.963 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PBX3	NM_006195.6	MANE Select	c.274+18076T>A		intron	N/A	NP_006186.1
	PBX3	NM_001411009.1		c.274+18076T>A		intron	N/A	NP_001397938.1
	PBX3	NM_001134778.2		c.49+18076T>A		intron	N/A	NP_001128250.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PBX3	ENST00000373489.10	TSL:1 MANE Select	c.274+18076T>A		intron	N/A	ENSP00000362588.5
	PBX3	ENST00000447726.6	TSL:1	c.49+18076T>A		intron	N/A	ENSP00000387456.2
	PBX3	ENST00000373482.6	TSL:1	n.274+18076T>A		intron	N/A	ENSP00000362581.2

Frequencies

GnomAD3 genomes AF: 0.900 AC: 136940 AN: 152082 Hom.: 61895 Cov.: 32

Gnomad AFR AF: 0.971

Gnomad AMI AF: 0.913

Gnomad AMR AF: 0.888

Gnomad ASJ AF: 0.869

Gnomad EAS AF: 0.905

Gnomad SAS AF: 0.930

Gnomad FIN AF: 0.902

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.858

Gnomad OTH AF: 0.912

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

GnomAD4 genome AF: 0.901 AC: 137069 AN: 152200 Hom.: 61962 Cov.: 32 AF XY: 0.904 AC XY: 67225 AN XY: 74394

African (AFR) AF: 0.971 AC: 40380 AN: 41574

American (AMR) AF: 0.889 AC: 13590 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.869 AC: 3015 AN: 3470

East Asian (EAS) AF: 0.906 AC: 4700 AN: 5188

South Asian (SAS) AF: 0.930 AC: 4483 AN: 4820

European-Finnish (FIN) AF: 0.902 AC: 9558 AN: 10596

Middle Eastern (MID) AF: 0.932 AC: 274 AN: 294

European-Non Finnish (NFE) AF: 0.858 AC: 58305 AN: 67938

Other (OTH) AF: 0.913 AC: 1931 AN: 2114

Alfa AF: 0.885 Hom.: 7506

Bravo AF: 0.902

Asia WGS AF: 0.907 AC: 3129 AN: 3452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	19
DANN	Benign	0.83
PhyloP100		6.7
Mutation Taster		=96/4	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: rs7040561; hg19: chr9-128528978;