rs121908190
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP3_StrongPP5
The NM_031433.4(MFRP):c.545T>C(p.Ile182Thr) variant causes a missense change. 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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I182M) has been classified as Uncertain significance.
Frequency
Genomes: not found (cov: 32)
Consequence
MFRP
NM_031433.4 missense
NM_031433.4 missense
Scores
4
7
5
Clinical Significance
Conservation
PhyloP100: 4.94
Genes affected
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 Likely_pathogenic. Variant got 7 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.982
PP5
?
Variant 11-119345516-A-G is Pathogenic according to our data. Variant chr11-119345516-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 4477.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-119345516-A-G is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MFRP | NM_031433.4 | c.545T>C | p.Ile182Thr | missense_variant | 5/15 | ENST00000619721.6 | |
C1QTNF5 | NM_015645.5 | c.-2092T>C | 5_prime_UTR_variant | 5/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MFRP | ENST00000619721.6 | c.545T>C | p.Ile182Thr | missense_variant | 5/15 | 1 | NM_031433.4 | P1 | |
MFRP | ENST00000360167.4 | c.545T>C | p.Ile182Thr | missense_variant | 5/10 | 2 | |||
MFRP | ENST00000529147.2 | n.508T>C | non_coding_transcript_exon_variant | 4/6 | 5 | ||||
MFRP | ENST00000634542.1 | c.*136T>C | 3_prime_UTR_variant, NMD_transcript_variant | 4/5 | 3 |
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
Alfa
AF:
Hom.:
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Nanophthalmos 2 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 05, 2005 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
H;H
MutationTaster
Benign
A;A;A;A
PrimateAI
Benign
T
Sift4G
Uncertain
D;D
Polyphen
P;.
Vest4
MutPred
Loss of stability (P = 0.039);Loss of stability (P = 0.039);
MVP
ClinPred
D
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