chr6-138218046-AG-A

Variant names:

• chr6-138218046-AG-A
• rs3841283
• NM_021635.3:c.349delC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_021635.3(PBOV1):​c.349delC​(p.Leu117fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PBOV1 NM_021635.3 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0220
• Publications: 0 publications found

Genes affected

PBOV1 (HGNC:21079): (prostate and breast cancer overexpressed 1) This intronless gene encodes a protein of unknown function. Its expression is up-regulated in some types of cancer, including prostate, breast, and bladder cancer. [provided by RefSeq, Aug 2011]

ARFGEF3 (HGNC:21213): (ARFGEF family member 3) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in actin cytoskeleton organization. Predicted to be located in transport vesicle membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021635.3. 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
	PBOV1	NM_021635.3	MANE Select	c.349delC	p.Leu117fs	frameshift	Exon 1 of 1	NP_067648.1
	ARFGEF3	NM_020340.5	MANE Select	c.351+8008delG		intron	N/A	NP_065073.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PBOV1	ENST00000527246.3	TSL:6 MANE Select	c.349delC	p.Leu117fs	frameshift	Exon 1 of 1	ENSP00000432353.1
	ARFGEF3	ENST00000251691.5	TSL:1 MANE Select	c.351+8008delG		intron	N/A	ENSP00000251691.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.022

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: rs3841283; hg19: chr6-138539183;