rs786201032
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PM2PM5PP3_StrongPP5_Very_Strong
The NM_001025295.3(IFITM5):c.119C>T(p.Ser40Leu) 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S40W) has been classified as Likely pathogenic.
Frequency
Consequence
NM_001025295.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IFITM5 | NM_001025295.3 | c.119C>T | p.Ser40Leu | missense_variant | 1/2 | ENST00000382614.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IFITM5 | ENST00000382614.2 | c.119C>T | p.Ser40Leu | missense_variant | 1/2 | 1 | NM_001025295.3 | P1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1443964Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 717030
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Dec 29, 2021 | Not observed in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 24293101, 28232077, 24519609, 24478195, 30039845, 28880886, 28548288, 27914223, 27678411, 27579219, 25387264, 30289614, 24715519, 29595812, 28319678, 31994750, 33942288, 33726816) - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2023 | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 40 of the IFITM5 protein (p.Ser40Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with osteogenesis imperfecta (PMID: 24478195, 24519609, 29595812). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 183677). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. For these reasons, this variant has been classified as Pathogenic. - |
Osteogenesis imperfecta type 5 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 01, 2014 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at