chr19-44649914-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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. 17/21 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
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -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 VariationId is 3785555.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006505.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PVR	NM_006505.5	MANE Select	c.533C>G	p.Thr178Ser	missense	Exon 3 of 8	NP_006496.4
	PVR	NM_001135770.4		c.533C>G	p.Thr178Ser	missense	Exon 3 of 6	NP_001129242.2	A0A0A0MSA9
	PVR	NM_001135768.3		c.533C>G	p.Thr178Ser	missense	Exon 3 of 8	NP_001129240.1	P15151-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PVR	ENST00000425690.8	TSL:1 MANE Select	c.533C>G	p.Thr178Ser	missense	Exon 3 of 8	ENSP00000402060.2	A0A0C4DG49
	PVR	ENST00000406449.8	TSL:1	c.533C>G	p.Thr178Ser	missense	Exon 3 of 6	ENSP00000383907.3	A0A0A0MSA9
	PVR	ENST00000971445.1		c.533C>G	p.Thr178Ser	missense	Exon 3 of 8	ENSP00000641504.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.51
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.82	N
PhyloP100		0.85
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.14	N
REVEL	Benign	0.19
Sift	Benign	0.86	T
Sift4G	Benign	1.0	T
Polyphen		0.028	B
Vest4		0.12
MutPred		0.64		Gain of disorder (P = 0.0401)
MVP		0.73
MPC		0.36
ClinPred		0.11	T
GERP RS		3.2
PromoterAI		0.055	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.19
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs946903753; hg19: chr19-45153186;