chr19-44653915-C-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The ENST00000425690.8(PVR):c.740C>T(p.Ser247Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
PVR
ENST00000425690.8 missense
ENST00000425690.8 missense
Scores
1
6
12
Clinical Significance
Conservation
PhyloP100: 2.14
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2740652).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PVR | NM_006505.5 | c.740C>T | p.Ser247Phe | missense_variant | 4/8 | ENST00000425690.8 | NP_006496.4 | |
PVR | NM_001135770.4 | c.740C>T | p.Ser247Phe | missense_variant | 4/6 | NP_001129242.2 | ||
PVR | NM_001135768.3 | c.740C>T | p.Ser247Phe | missense_variant | 4/8 | NP_001129240.1 | ||
PVR | NM_001135769.3 | c.740C>T | p.Ser247Phe | missense_variant | 4/7 | NP_001129241.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PVR | ENST00000425690.8 | c.740C>T | p.Ser247Phe | missense_variant | 4/8 | 1 | NM_006505.5 | ENSP00000402060 | P2 | |
CEACAM16-AS1 | ENST00000662585.1 | n.476-21296G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251372Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135858
GnomAD3 exomes
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1458892Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 725958
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ExAC
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1
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 04, 2022 | The c.740C>T (p.S247F) alteration is located in exon 4 (coding exon 4) of the PVR gene. This alteration results from a C to T substitution at nucleotide position 740, causing the serine (S) at amino acid position 247 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M;M;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D
REVEL
Benign
Sift
Benign
T;T;T;T
Sift4G
Pathogenic
D;D;D;D
Polyphen
0.13, 0.69
.;B;P;.
Vest4
MutPred
Gain of catalytic residue at S247 (P = 0.0405);Gain of catalytic residue at S247 (P = 0.0405);Gain of catalytic residue at S247 (P = 0.0405);Gain of catalytic residue at S247 (P = 0.0405);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
gMVP
Splicing
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Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at