6-138218046-AG-AGG

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_021635.3(PBOV1):​c.349dupC​(p.Leu117ProfsTer33) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0863 in 1,613,418 control chromosomes in the GnomAD database, including 8,837 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (1314 hom., cov: 31)
  • Exomes 𝑓: 0.083 (7523 hom.)
• Consequence: PBOV1 NM_021635.3 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0220
• Publications: 9 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: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PBOV1	NM_021635.3	c.349dupC	p.Leu117ProfsTer33	frameshift_variant	Exon 1 of 1	ENST00000527246.3	NP_067648.1
ARFGEF3	NM_020340.5	c.351+8008dupG		intron_variant	Intron 4 of 33	ENST00000251691.5	NP_065073.3
ARFGEF3	XR_001743524.2	n.499+8008dupG		intron_variant	Intron 4 of 34

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PBOV1	ENST00000527246.3	c.349dupC	p.Leu117ProfsTer33	frameshift_variant	Exon 1 of 1	6	NM_021635.3	ENSP00000432353.1
ARFGEF3	ENST00000251691.5	c.351+8008dupG		intron_variant	Intron 4 of 33	1	NM_020340.5	ENSP00000251691.4

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17123 AN: 152040 Hom.: 1297 Cov.: 31

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.0700

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.0691

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0694

Gnomad OTH AF: 0.0994

GnomAD2 exomes AF: 0.119 AC: 29755 AN: 250830 AF XY: 0.108

Gnomad AFR exome AF: 0.159

Gnomad AMR exome AF: 0.214

Gnomad ASJ exome AF: 0.0634

Gnomad EAS exome AF: 0.368

Gnomad FIN exome AF: 0.118

Gnomad NFE exome AF: 0.0653

Gnomad OTH exome AF: 0.0927

GnomAD4 exome AF: 0.0835 AC: 121996 AN: 1461260 Hom.: 7523 Cov.: 31 AF XY: 0.0818 AC XY: 59448 AN XY: 726924

African (AFR) AF: 0.160 AC: 5371 AN: 33478

American (AMR) AF: 0.207 AC: 9267 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0671 AC: 1754 AN: 26126

East Asian (EAS) AF: 0.360 AC: 14275 AN: 39682

South Asian (SAS) AF: 0.0626 AC: 5395 AN: 86234

European-Finnish (FIN) AF: 0.111 AC: 5929 AN: 53398

Middle Eastern (MID) AF: 0.0626 AC: 361 AN: 5766

European-Non Finnish (NFE) AF: 0.0668 AC: 74262 AN: 1111492

Other (OTH) AF: 0.0892 AC: 5382 AN: 60364

GnomAD4 genome AF: 0.113 AC: 17177 AN: 152158 Hom.: 1314 Cov.: 31 AF XY: 0.115 AC XY: 8568 AN XY: 74394

African (AFR) AF: 0.156 AC: 6479 AN: 41500

American (AMR) AF: 0.137 AC: 2097 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0700 AC: 243 AN: 3472

East Asian (EAS) AF: 0.359 AC: 1850 AN: 5160

South Asian (SAS) AF: 0.0690 AC: 333 AN: 4828

European-Finnish (FIN) AF: 0.115 AC: 1222 AN: 10606

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0695 AC: 4723 AN: 67984

Other (OTH) AF: 0.0993 AC: 210 AN: 2114

Alfa AF: 0.0839 Hom.: 545

Bravo AF: 0.121

Asia WGS AF: 0.180 AC: 625 AN: 3478

EpiCase AF: 0.0631

EpiControl AF: 0.0580

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.022
Mutation Taster		=187/13	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: rs3841283; hg19: chr6-138539183; COSMIC: COSV52450632;