chr19-44647372-G-T

Position:

• chr19-44647372-G-T

Variant summary

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

The ENST00000425690.8(PVR):​c.229G>T​(p.Val77Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: PVR ENST00000425690.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.46

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 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/exons	MANE	Protein	UniProt
PVR	NM_006505.5	c.229G>T	p.Val77Phe	missense_variant	2/8	ENST00000425690.8	NP_006496.4
PVR	NM_001135770.4	c.229G>T	p.Val77Phe	missense_variant	2/6		NP_001129242.2
PVR	NM_001135768.3	c.229G>T	p.Val77Phe	missense_variant	2/8		NP_001129240.1
PVR	NM_001135769.3	c.229G>T	p.Val77Phe	missense_variant	2/7		NP_001129241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PVR	ENST00000425690.8	c.229G>T	p.Val77Phe	missense_variant	2/8	1	NM_006505.5	ENSP00000402060	P2
CEACAM16-AS1	ENST00000662585.1	n.476-14753C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 30

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2022

The c.229G>T (p.V77F) alteration is located in exon 2 (coding exon 2) of the PVR gene. This alteration results from a G to T substitution at nucleotide position 229, causing the valine (V) at amino acid position 77 to be replaced by a phenylalanine (F). 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	Benign	0.23
BayesDel_addAF	Benign	0.0033	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.094	T;.;.;T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.42
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.73	T;T;T;T
M_CAP	Benign	0.051	D
MetaRNN	Uncertain	0.49	T;T;T;T
MetaSVM	Benign	-0.60	T
MutationAssessor	Uncertain	2.3	.;M;M;.
MutationTaster	Benign	0.77	N;N;N;N
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.5	D;D;D;D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0020	D;D;D;D
Sift4G	Uncertain	0.0040	D;D;D;D
Polyphen		0.95, 0.97	.;P;D;.
Vest4		0.45
MutPred		0.63		Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);Gain of sheet (P = 0.1208);
MVP		0.75
MPC		1.3
ClinPred		0.92	D
GERP RS		1.2
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs558066119; hg19: chr19-45150644;