rs786205904
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP2PP3_ModeratePP5
The NM_004736.4(XPR1):c.653T>C(p.Leu218Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
XPR1
NM_004736.4 missense
NM_004736.4 missense
Scores
15
3
1
Clinical Significance
Conservation
PhyloP100: 7.41
Genes affected
XPR1 (HGNC:12827): (xenotropic and polytropic retrovirus receptor 1) The protein encoded by this gene is a receptor for the xenotropic and polytropic classes of murine leukemia viruses. The encoded protein is involved in phosphate homeostasis by mediating phosphate export from the cell. Defects in this gene have been associated with idiopathic basal ganglia calcification-6. [provided by RefSeq, Jun 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PM1
?
In a topological_domain Cytoplasmic (size 235) in uniprot entity XPR1_HUMAN there are 6 pathogenic changes around while only 1 benign (86%) in NM_004736.4
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, XPR1
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.9
PP5
?
Variant 1-180806529-T-C is Pathogenic according to our data. Variant chr1-180806529-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 192306.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
XPR1 | NM_004736.4 | c.653T>C | p.Leu218Ser | missense_variant | 6/15 | ENST00000367590.9 | |
XPR1 | NM_001135669.2 | c.653T>C | p.Leu218Ser | missense_variant | 6/14 | ||
XPR1 | NM_001328662.2 | c.653T>C | p.Leu218Ser | missense_variant | 6/11 | ||
XPR1 | NR_137330.2 | n.833T>C | non_coding_transcript_exon_variant | 6/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
XPR1 | ENST00000367590.9 | c.653T>C | p.Leu218Ser | missense_variant | 6/15 | 1 | NM_004736.4 | P1 | |
XPR1 | ENST00000367589.3 | c.653T>C | p.Leu218Ser | missense_variant | 6/14 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Basal ganglia calcification, idiopathic, 6 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 01, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Pathogenic
D;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;H
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MutPred
Gain of disorder (P = 0.0039);Gain of disorder (P = 0.0039);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at