NM_006505.5:c.533C>G

Variant names:

• chr19-44649914-C-G
• rs946903753
• NM_006505.5:c.533C>G

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2 BP4 BP6_Moderate

The NM_006505.5(PVR):​c.533C>G​(p.Thr178Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: PVR NM_006505.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.854

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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.281146).
• BP6: Variant 19-44649914-C-G is Benign according to our data. Variant chr19-44649914-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3785555.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.533C>G	p.Thr178Ser	missense_variant	Exon 3 of 8	ENST00000425690.8	NP_006496.4
PVR	NM_001135770.4	c.533C>G	p.Thr178Ser	missense_variant	Exon 3 of 6		NP_001129242.2
PVR	NM_001135768.3	c.533C>G	p.Thr178Ser	missense_variant	Exon 3 of 8		NP_001129240.1
PVR	NM_001135769.3	c.533C>G	p.Thr178Ser	missense_variant	Exon 3 of 7		NP_001129241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PVR	ENST00000425690.8	c.533C>G	p.Thr178Ser	missense_variant	Exon 3 of 8	1	NM_006505.5	ENSP00000402060.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 23, 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	0.081
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	8.3
DANN	Benign	0.24
DEOGEN2	Benign	0.0095	T;.;.;T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.51
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.48	T;T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.28	T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.82	.;N;N;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.14	N;N;N;N
REVEL	Benign	0.19
Sift	Benign	0.86	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.028, 0.10	.;B;B;.
Vest4		0.12
MutPred		0.64		Gain of disorder (P = 0.0401);Gain of disorder (P = 0.0401);Gain of disorder (P = 0.0401);Gain of disorder (P = 0.0401);
MVP		0.73
MPC		0.36
ClinPred		0.11	T
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.19

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

Other links and lift over

dbSNP: rs946903753; hg19: chr19-45153186;