5-38885400-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_003999.3(OSMR):c.755C>G(p.Thr252Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,518 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
OSMR
NM_003999.3 missense
NM_003999.3 missense
Scores
4
14
Clinical Significance
Conservation
PhyloP100: 2.38
Genes affected
OSMR (HGNC:8507): (oncostatin M receptor) This gene encodes a member of the type I cytokine receptor family. The encoded protein heterodimerizes with interleukin 6 signal transducer to form the type II oncostatin M receptor and with interleukin 31 receptor A to form the interleukin 31 receptor, and thus transduces oncostatin M and interleukin 31 induced signaling events. Mutations in this gene have been associated with familial primary localized cutaneous amyloidosis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2009]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OSMR | NM_003999.3 | c.755C>G | p.Thr252Ser | missense_variant | 6/18 | ENST00000274276.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OSMR | ENST00000274276.8 | c.755C>G | p.Thr252Ser | missense_variant | 6/18 | 1 | NM_003999.3 | P1 | |
OSMR | ENST00000502536.5 | c.755C>G | p.Thr252Ser | missense_variant | 6/7 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251072Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135698
GnomAD3 exomes
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GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461518Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727112
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ExAC
?
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1
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 06, 2022 | The c.755C>G (p.T252S) alteration is located in exon 6 (coding exon 5) of the OSMR gene. This alteration results from a C to G substitution at nucleotide position 755, causing the threonine (T) at amino acid position 252 to be replaced by a serine (S). 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
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Uncertain
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;D
Polyphen
P;P
Vest4
MutPred
Gain of disorder (P = 0.0627);Gain of disorder (P = 0.0627);
MVP
MPC
0.38
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at