19-44647256-C-G

Variant names:

• chr19-44647256-C-G
• rs1414330505
• NM_006505.5:c.113C>G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_006505.5(PVR):​c.113C>G​(p.Pro38Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000129 in 1,553,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 30)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: PVR NM_006505.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.18

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]

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

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.024058044).
• BP6: Variant 19-44647256-C-G is Benign according to our data. Variant chr19-44647256-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3785554.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PVR	NM_006505.5	c.113C>G	p.Pro38Arg	missense_variant	Exon 2 of 8	ENST00000425690.8	NP_006496.4
PVR	NM_001135770.4	c.113C>G	p.Pro38Arg	missense_variant	Exon 2 of 6		NP_001129242.2
PVR	NM_001135768.3	c.113C>G	p.Pro38Arg	missense_variant	Exon 2 of 8		NP_001129240.1
PVR	NM_001135769.3	c.113C>G	p.Pro38Arg	missense_variant	Exon 2 of 7		NP_001129241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PVR	ENST00000425690.8	c.113C>G	p.Pro38Arg	missense_variant	Exon 2 of 8	1	NM_006505.5	ENSP00000402060.2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152186 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1400932 Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1 AN XY: 690590

Gnomad4 AFR exome AF: 0.0000314

Gnomad4 AMR exome AF: 0.00

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: 0.00000657 AC: 1 AN: 152186 Hom.: 0 Cov.: 30 AF XY: 0.0000135 AC XY: 1 AN XY: 74342

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

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: 0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 22, 2025

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.0030
DANN	Benign	0.75
DEOGEN2	Benign	0.0056	T;.;.;T
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.0022	N
LIST_S2	Benign	0.56	T;T;T;T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.024	T;T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	-2.1	.;N;N;.
PrimateAI	Benign	0.34	T
PROVEAN	Benign	2.6	N;N;N;N
REVEL	Benign	0.078
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0	.;B;B;.
Vest4		0.046
MutPred		0.46		Loss of glycosylation at T35 (P = 0.0224);Loss of glycosylation at T35 (P = 0.0224);Loss of glycosylation at T35 (P = 0.0224);Loss of glycosylation at T35 (P = 0.0224);
MVP		0.34
MPC		0.37
ClinPred		0.057	T
GERP RS		-9.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

Other links and lift over

dbSNP: rs1414330505; hg19: chr19-45150528;