rs1555036138
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 5P and 1B. PM1PM2PP5BP4
The NM_001278431.2(C1QTNF5):c.556C>T(p.Pro186Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
C1QTNF5
NM_001278431.2 missense
NM_001278431.2 missense
Scores
2
16
Clinical Significance
Conservation
PhyloP100: 3.82
Genes affected
C1QTNF5 (HGNC:14344): (C1q and TNF related 5) This gene encodes a member of a family of proteins that function as components of basement membranes and may play a role in cell adhesion. Mutations in this gene have been associated with late-onset retinal degeneration. The protein may be encoded by either a bicistronic transcript including sequence from the upstream membrane frizzled-related protein gene (MFRP), or by a monocistronic transcript expressed from an internal promoter. [provided by RefSeq, Jun 2013]
MFRP (HGNC:18121): (membrane frizzled-related protein) This gene encodes a member of the frizzled-related protein family. The encoded protein plays an important role in eye development and mutations in this gene have been associated with nanophthalmos, posterior microphthalmia, retinitis pigmentosa, foveoschisis, and optic disc drusen. The protein is encoded by a bicistronic transcript which also encodes C1q and tumor necrosis factor related protein 5 (C1QTNF5). [provided by RefSeq, Jun 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM1
?
In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 5 uncertain in NM_001278431.2
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 11-119339507-G-A is Pathogenic according to our data. Variant chr11-119339507-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 438182.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-119339507-G-A is described in Lovd as [Likely_pathogenic].
BP4
?
Computational evidence support a benign effect (MetaRNN=0.21386418). . Strength limited to SUPPORTING due to the PP5.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
C1QTNF5 | NM_001278431.2 | c.556C>T | p.Pro186Ser | missense_variant | 3/3 | ENST00000528368.3 | |
MFRP | NM_031433.4 | c.*1452C>T | 3_prime_UTR_variant | 15/15 | ENST00000619721.6 | ||
C1QTNF5 | NM_015645.5 | c.556C>T | p.Pro186Ser | missense_variant | 15/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
C1QTNF5 | ENST00000528368.3 | c.556C>T | p.Pro186Ser | missense_variant | 3/3 | 1 | NM_001278431.2 | P1 | |
C1QTNF5 | ENST00000530681.2 | c.556C>T | p.Pro186Ser | missense_variant | 2/2 | 1 | P1 | ||
MFRP | ENST00000619721.6 | c.*1452C>T | 3_prime_UTR_variant | 15/15 | 1 | NM_031433.4 | P1 | ||
C1QTNF5 | ENST00000525657.2 | n.446C>T | non_coding_transcript_exon_variant | 2/2 | 2 |
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: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Retinal dystrophy Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | NIHR Bioresource Rare Diseases, University of Cambridge | Jan 01, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.
REVEL
Benign
Sift
Benign
T;.
Sift4G
Benign
T;T
Vest4
MutPred
Loss of glycosylation at P186 (P = 0.0554);Loss of glycosylation at P186 (P = 0.0554);
MVP
ClinPred
T
GERP RS
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