5-38885349-A-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_003999.3(OSMR):c.704A>C(p.Lys235Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,680 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000068 ( 0 hom. )
Consequence
OSMR
NM_003999.3 missense, splice_region
NM_003999.3 missense, splice_region
Scores
10
8
Splicing: ADA: 0.5291
2
Clinical Significance
Conservation
PhyloP100: 2.87
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.704A>C | p.Lys235Thr | missense_variant, splice_region_variant | 6/18 | ENST00000274276.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OSMR | ENST00000274276.8 | c.704A>C | p.Lys235Thr | missense_variant, splice_region_variant | 6/18 | 1 | NM_003999.3 | P1 | |
OSMR | ENST00000502536.5 | c.704A>C | p.Lys235Thr | missense_variant, splice_region_variant | 6/7 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152220Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000399 AC: 10AN: 250918Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135622
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GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461460Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 727066
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152220Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74368
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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 | Apr 19, 2023 | The c.704A>C (p.K235T) alteration is located in exon 6 (coding exon 5) of the OSMR gene. This alteration results from a A to C substitution at nucleotide position 704, causing the lysine (K) at amino acid position 235 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
D
MetaRNN
Uncertain
T;T
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Benign
T;T
Sift4G
Uncertain
D;T
Polyphen
D;D
Vest4
MutPred
Loss of methylation at K235 (P = 0.016);Loss of methylation at K235 (P = 0.016);
MVP
MPC
0.43
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 3
Find out detailed SpliceAI scores and Pangolin per-transcript scores at