Variant chr6-138218163-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_021635.3(PBOV1):c.233A>G(p.His78Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000384 in 1,613,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H78L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

PBOV1
NM_021635.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.590

Variant links:

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]

PBOV1 links:

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]

ARFGEF3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.040208638).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PBOV1	NM_021635.3 linkuse as main transcript	c.233A>G	p.His78Arg	missense_variant	1/1	ENST00000527246.3
ARFGEF3	NM_020340.5 linkuse as main transcript	c.351+8122T>C		intron_variant		ENST00000251691.5
ARFGEF3	XR_001743524.2 linkuse as main transcript	n.499+8122T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PBOV1	ENST00000527246.3 linkuse as main transcript	c.233A>G	p.His78Arg	missense_variant	1/1		NM_021635.3	P1
ARFGEF3	ENST00000251691.5 linkuse as main transcript	c.351+8122T>C		intron_variant		1	NM_020340.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000598

AC:

AN:

251006

Hom.:

AF XY:

0.0000516

AC XY:

AN XY:

135642

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000435

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.0000349

AC:

AN:

1461620

Hom.:

Cov.:

AF XY:

0.0000316

AC XY:

AN XY:

727090

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000563

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152240

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000384

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000102

Hom.:

Bravo

AF:

0.0000982

ExAC

AF:

0.0000412

AC:

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2023

The c.233A>G (p.H78R) alteration is located in exon 1 (coding exon 1) of the PBOV1 gene. This alteration results from a A to G substitution at nucleotide position 233, causing the histidine (H) at amino acid position 78 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.89

DANN

Benign

0.76

DEOGEN2

Benign

0.043

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0039

M_CAP

Benign

0.0044

MetaRNN

Benign

0.040

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.23

PROVEAN

Pathogenic

-8.0

REVEL

Benign

0.11

Polyphen

0.0080

Vest4

0.088

MVP

0.12

MPC

0.0044

ClinPred

0.017

GERP RS

1.7

Varity_R

0.45

gMVP

0.0045

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over