chr9-125748621-CA-C

Variant names:

• chr9-125748621-CA-C
• NM_006195.6:c.273delA

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_006195.6(PBX3):​c.273delA​(p.Gly92ValfsTer17) variant causes a frameshift, splice region change. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PBX3 NM_006195.6 frameshift, splice_region
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.96
• Publications: 0 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: Pathogenic. The variant received 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 9-125748621-CA-C is Pathogenic according to our data. Variant chr9-125748621-CA-C is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 2430149.Status of the report is no_assertion_criteria_provided, 0 stars.

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.273delA	p.Gly92ValfsTer17	frameshift splice_region	Exon 2 of 9	NP_006186.1	P40426-1
	PBX3	NM_001411009.1		c.273delA	p.Gly92ValfsTer17	frameshift splice_region	Exon 2 of 10	NP_001397938.1	Q5JS98
	PBX3	NM_001134778.2		c.48delA	p.Gly17ValfsTer17	frameshift splice_region	Exon 2 of 9	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.273delA	p.Gly92ValfsTer17	frameshift splice_region	Exon 2 of 9	ENSP00000362588.5	P40426-1
	PBX3	ENST00000447726.6	TSL:1	c.48delA	p.Gly17ValfsTer17	frameshift splice_region	Exon 2 of 9	ENSP00000387456.2	P40426-5
	PBX3	ENST00000373482.6	TSL:1	n.273delA		splice_region non_coding_transcript_exon	Exon 2 of 8	ENSP00000362581.2	H3BLX0

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	X-linked cone-rod dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.0

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

Other links and lift over

hg19: chr9-128510900;