19-44649934-G-A

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006505.5(PVR):c.553G>A(p.Gly185Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,612,166 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

PVR
NM_006505.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.253

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PVR	NM_006505.5 link	c.553G>A	p.Gly185Arg	missense_variant	Exon 3 of 8	ENST00000425690.8	NP_006496.4	P15151A0A0C4DG49A8K4I1
PVR	NM_001135770.4 link	c.553G>A	p.Gly185Arg	missense_variant	Exon 3 of 6		NP_001129242.2	P15151A0A0A0MSA9
PVR	NM_001135768.3 link	c.553G>A	p.Gly185Arg	missense_variant	Exon 3 of 8		NP_001129240.1	P15151-2
PVR	NM_001135769.3 link	c.553G>A	p.Gly185Arg	missense_variant	Exon 3 of 7		NP_001129241.1	P15151-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PVR	ENST00000425690.8 link	c.553G>A	p.Gly185Arg	missense_variant	Exon 3 of 8	1	NM_006505.5	ENSP00000402060.2		A0A0C4DG49

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000241

AC:

AN:

248856

Hom.:

AF XY:

0.0000223

AC XY:

AN XY:

134584

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000117

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:

0.00000890

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000178

AC:

AN:

1459856

Hom.:

Cov.:

AF XY:

0.0000152

AC XY:

AN XY:

726000

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000135

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.0000498

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152310

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.553G>A (p.G185R) alteration is located in exon 3 (coding exon 3) of the PVR gene. This alteration results from a G to A substitution at nucleotide position 553, causing the glycine (G) at amino acid position 185 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

Uncertain

0.39

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

T;.;.;T

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.66

T;T;T;T

M_CAP

Benign

0.042

MetaRNN

Uncertain

0.44

T;T;T;T

MetaSVM

Benign

-0.47

MutationAssessor

Pathogenic

3.2

.;M;M;.

PrimateAI

Benign

0.25

PROVEAN

Pathogenic

-4.7

D;D;D;D

REVEL

Benign

0.22

Sift

Uncertain

0.0070

D;D;D;D

Sift4G

Uncertain

0.038

D;D;D;D

Polyphen

1.0, 0.98

.;D;D;.

Vest4

0.14

MutPred

0.75

Gain of MoRF binding (P = 0.0625);Gain of MoRF binding (P = 0.0625);Gain of MoRF binding (P = 0.0625);Gain of MoRF binding (P = 0.0625);

MVP

0.87

MPC

0.90

ClinPred

0.83

GERP RS

-0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.54

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