chr19-44650064-T-C

Position:

chr19-44650064-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000425690.8(PVR):c.683T>C(p.Phe228Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000903 in 1,550,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000064 ( 0 hom. )

Consequence

PVR
ENST00000425690.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.13

Variant links:

Genes affected

PVR (HGNC:9705): (PVR cell adhesion molecule) The protein encoded by this gene is a transmembrane glycoprotein belonging to the immunoglobulin superfamily. The external domain mediates cell attachment to the extracellular matrix molecule vitronectin, while its intracellular domain interacts with the dynein light chain Tctex-1/DYNLT1. The gene is specific to the primate lineage, and serves as a cellular receptor for poliovirus in the first step of poliovirus replication. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

PVR links:

CEACAM16-AS1 (HGNC:55317): (CEACAM16, CEACAM19 and PVR antisense RNA 1)

CEACAM16-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16008359).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PVR	NM_006505.5 linkuse as main transcript	c.683T>C	p.Phe228Ser	missense_variant	3/8	ENST00000425690.8	NP_006496.4
PVR	NM_001135770.4 linkuse as main transcript	c.683T>C	p.Phe228Ser	missense_variant	3/6		NP_001129242.2
PVR	NM_001135768.3 linkuse as main transcript	c.683T>C	p.Phe228Ser	missense_variant	3/8		NP_001129240.1
PVR	NM_001135769.3 linkuse as main transcript	c.683T>C	p.Phe228Ser	missense_variant	3/7		NP_001129241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PVR	ENST00000425690.8 linkuse as main transcript	c.683T>C	p.Phe228Ser	missense_variant	3/8	1	NM_006505.5	ENSP00000402060	P2
CEACAM16-AS1	ENST00000662585.1 linkuse as main transcript	n.476-17445A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000404

AC:

AN:

198054

Hom.:

AF XY:

0.0000381

AC XY:

AN XY:

105076

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000303

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000644

AC:

AN:

1398548

Hom.:

Cov.:

AF XY:

0.00000726

AC XY:

AN XY:

688584

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000248

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000264

ExAC

AF:

0.00000828

AC:

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

Jul 15, 2021

The c.683T>C (p.F228S) alteration is located in exon 3 (coding exon 3) of the PVR gene. This alteration results from a T to C substitution at nucleotide position 683, causing the phenylalanine (F) at amino acid position 228 to be replaced by a serine (S). 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

0.28

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.030

T;.;.;T

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.26

LIST_S2

Uncertain

0.88

D;D;D;D

M_CAP

Benign

0.0072

MetaRNN

Benign

0.16

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.1

.;M;M;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-3.9

D;D;D;D

REVEL

Benign

0.070

Sift

Uncertain

0.017

D;D;D;D

Sift4G

Uncertain

0.012

D;D;D;D

Polyphen

0.98, 0.77

.;D;P;.

Vest4

0.31

MutPred

0.58

Gain of disorder (P = 0.0078);Gain of disorder (P = 0.0078);Gain of disorder (P = 0.0078);Gain of disorder (P = 0.0078);

MVP

0.42

MPC

1.4

ClinPred

0.36

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.50

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

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