chr22-30264106-G-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_020530.6(OSM):ā€‹c.536C>Gā€‹(p.Thr179Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000621 in 1,610,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000055 ( 0 hom. )

Consequence

OSM
NM_020530.6 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.881
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 Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.07135326).
BS2
High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OSMNM_020530.6 linkuse as main transcriptc.536C>G p.Thr179Ser missense_variant 3/3 ENST00000215781.3
OSMNM_001319108.2 linkuse as main transcriptc.473C>G p.Thr158Ser missense_variant 3/3
OSMXM_047441387.1 linkuse as main transcriptc.473C>G p.Thr158Ser missense_variant 3/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OSMENST00000215781.3 linkuse as main transcriptc.536C>G p.Thr179Ser missense_variant 3/31 NM_020530.6 P2
OSMENST00000403389.1 linkuse as main transcriptc.473C>G p.Thr158Ser missense_variant 3/33 A2
OSMENST00000403463.1 linkuse as main transcriptc.*330C>G 3_prime_UTR_variant 2/23

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152228
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000403
AC:
1
AN:
248006
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
134594
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000897
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000549
AC:
8
AN:
1458464
Hom.:
0
Cov.:
31
AF XY:
0.00000552
AC XY:
4
AN XY:
724954
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000721
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152228
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1

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 GeneticsApr 29, 2024The c.536C>G (p.T179S) alteration is located in exon 3 (coding exon 3) of the OSM gene. This alteration results from a C to G substitution at nucleotide position 536, causing the threonine (T) at amino acid position 179 to be replaced by a serine (S). 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
0.12
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
4.1
DANN
Benign
0.41
DEOGEN2
Uncertain
0.49
T;.
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.12
N
LIST_S2
Benign
0.25
T;T
M_CAP
Benign
0.041
D
MetaRNN
Benign
0.071
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-1.7
N;N
REVEL
Benign
0.085
Sift
Benign
0.12
T;T
Sift4G
Benign
0.19
T;T
Polyphen
0.0060
B;.
Vest4
0.040
MutPred
0.46
Gain of relative solvent accessibility (P = 0.0098);.;
MVP
0.32
MPC
0.21
ClinPred
0.061
T
GERP RS
-0.75
Varity_R
0.048
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: rs749126315; hg19: chr22-30660095; API