22-30264133-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_020530.6(OSM):​c.509G>A​(p.Arg170Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,612,370 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

OSM
NM_020530.6 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.404
Variant links:
Genes affected
OSM (HGNC:8506): (oncostatin M) This gene encodes a member of the leukemia inhibitory factor/oncostatin-M (LIF/OSM) family of proteins. The encoded preproprotein is proteolytically processed to generate the mature protein. This protein is a secreted cytokine and growth regulator that inhibits the proliferation of a number of tumor cell lines. This protein also regulates the production of other cytokines, including interleukin 6, granulocyte-colony stimulating factor and granulocyte-macrophage colony stimulating factor in endothelial cells. This gene and the related gene, leukemia inhibitory factor, also present on chromosome 22, may have resulted from the duplication of a common ancestral gene. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Jan 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.047400534).
BS2
High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OSMNM_020530.6 linkuse as main transcriptc.509G>A p.Arg170Gln missense_variant 3/3 ENST00000215781.3 NP_065391.1 P13725
OSMNM_001319108.2 linkuse as main transcriptc.446G>A p.Arg149Gln missense_variant 3/3 NP_001306037.1 P13725B5MCX1
OSMXM_047441387.1 linkuse as main transcriptc.446G>A p.Arg149Gln missense_variant 3/3 XP_047297343.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OSMENST00000215781.3 linkuse as main transcriptc.509G>A p.Arg170Gln missense_variant 3/31 NM_020530.6 ENSP00000215781.2 P13725
OSMENST00000403389.1 linkuse as main transcriptc.446G>A p.Arg149Gln missense_variant 3/33 ENSP00000383893.1 B5MCX1
OSMENST00000403463.1 linkuse as main transcriptc.*303G>A 3_prime_UTR_variant 2/23 ENSP00000384543.1 B5MC70

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152242
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000361
AC:
9
AN:
249248
Hom.:
0
AF XY:
0.0000370
AC XY:
5
AN XY:
135138
show subpopulations
Gnomad AFR exome
AF:
0.0000627
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000327
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000891
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000822
AC:
12
AN:
1460128
Hom.:
0
Cov.:
31
AF XY:
0.00000689
AC XY:
5
AN XY:
726110
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000720
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152242
Hom.:
0
Cov.:
33
AF XY:
0.0000538
AC XY:
4
AN XY:
74382
show subpopulations
Gnomad4 AFR
AF:
0.000121
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189
ExAC
AF:
0.0000659
AC:
8
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 24, 2023The c.509G>A (p.R170Q) alteration is located in exon 3 (coding exon 3) of the OSM gene. This alteration results from a G to A substitution at nucleotide position 509, causing the arginine (R) at amino acid position 170 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.082
BayesDel_addAF
Benign
-0.53
T
BayesDel_noAF
Benign
-0.69
CADD
Benign
8.1
DANN
Benign
0.97
DEOGEN2
Benign
0.23
T;.
Eigen
Benign
-0.86
Eigen_PC
Benign
-0.97
FATHMM_MKL
Benign
0.044
N
LIST_S2
Benign
0.53
T;T
M_CAP
Benign
0.0098
T
MetaRNN
Benign
0.047
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.34
N;.
PrimateAI
Benign
0.21
T
PROVEAN
Benign
0.66
N;N
REVEL
Benign
0.031
Sift
Benign
0.24
T;T
Sift4G
Benign
0.16
T;T
Polyphen
0.89
P;.
Vest4
0.049
MVP
0.46
MPC
0.30
ClinPred
0.025
T
GERP RS
1.2
Varity_R
0.025
gMVP
0.14

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs776077012; hg19: chr22-30660122; API