chr19-44647286-C-T

Variant names:

• chr19-44647286-C-T
• rs1973150285
• NM_006505.5:c.143C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_006505.5(PVR):​c.143C>T​(p.Pro48Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000489 in 1,431,274 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: PVR NM_006505.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.143
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.143C>T	p.Pro48Leu	missense	Exon 2 of 8	NP_006496.4
	PVR	NM_001135770.4		c.143C>T	p.Pro48Leu	missense	Exon 2 of 6	NP_001129242.2	A0A0A0MSA9
	PVR	NM_001135768.3		c.143C>T	p.Pro48Leu	missense	Exon 2 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.143C>T	p.Pro48Leu	missense	Exon 2 of 8	ENSP00000402060.2	A0A0C4DG49
	PVR	ENST00000406449.8	TSL:1	c.143C>T	p.Pro48Leu	missense	Exon 2 of 6	ENSP00000383907.3	A0A0A0MSA9
	PVR	ENST00000971445.1		c.143C>T	p.Pro48Leu	missense	Exon 2 of 8	ENSP00000641504.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000489 AC: 7 AN: 1431274 Hom.: 0 Cov.: 32 AF XY: 0.00000564 AC XY: 4 AN XY: 708986

African (AFR) AF: 0.00 AC: 0 AN: 32802

American (AMR) AF: 0.00 AC: 0 AN: 39584

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25530

East Asian (EAS) AF: 0.00 AC: 0 AN: 38054

South Asian (SAS) AF: 0.00 AC: 0 AN: 82192

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51218

Middle Eastern (MID) AF: 0.000698 AC: 4 AN: 5730

European-Non Finnish (NFE) AF: 0.00000274 AC: 3 AN: 1096884

Other (OTH) AF: 0.00 AC: 0 AN: 59280

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.20
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.056	D
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.59	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		-0.14
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-7.2	D
REVEL	Benign	0.19
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.010	D
Polyphen		0.99	D
Vest4		0.31
MutPred		0.70		Loss of catalytic residue at P48 (P = 0.0287)
MVP		0.76
MPC		1.0
ClinPred		0.90	D
GERP RS		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.71
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.20		Position offset: 14

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1973150285; hg19: chr19-45150558;