Genetic Variant NM_020530.6:c.638G>C (chr22-30264004-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020530.6(OSM):c.638G>C(p.Gly213Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000213 in 1,406,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G213E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

OSM
NM_020530.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.01

Publications

0 publications found

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]

OSM links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08317977).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020530.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSM	NM_020530.6	MANE Select	c.638G>C	p.Gly213Ala	missense	Exon 3 of 3	NP_065391.1	P13725
	OSM	NM_001319108.2		c.575G>C	p.Gly192Ala	missense	Exon 3 of 3	NP_001306037.1	B5MCX1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OSM	ENST00000215781.3	TSL:1 MANE Select	c.638G>C	p.Gly213Ala	missense	Exon 3 of 3	ENSP00000215781.2	P13725
OSM	ENST00000403389.1	TSL:3	c.575G>C	p.Gly192Ala	missense	Exon 3 of 3	ENSP00000383893.1	B5MCX1
OSM	ENST00000403463.1	TSL:3	c.*432G>C		downstream_gene	N/A	ENSP00000384543.1	B5MC70

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000480

AC:

AN:

208520

AF XY:

0.00000904

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000105

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000213

AC:

AN:

1406520

Hom.:

Cov.:

AF XY:

0.00000433

AC XY:

AN XY:

693094

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31990

American (AMR)

AF:

0.00

AC:

AN:

38972

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22174

East Asian (EAS)

AF:

0.00

AC:

AN:

39210

South Asian (SAS)

AF:

0.00

AC:

AN:

77158

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50956

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5478

European-Non Finnish (NFE)

AF:

0.00000277

AC:

AN:

1082602

Other (OTH)

AF:

0.00

AC:

AN:

57980

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000826

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.065

(source)

DANN

Benign

0.71

DEOGEN2

Uncertain

0.78

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.36

M_CAP

Benign

0.011

MetaRNN

Benign

0.083

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

PhyloP100

-2.0

PrimateAI

Benign

0.23

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.034

Sift

Benign

0.17

Sift4G

Benign

0.089

Polyphen

0.025

Vest4

0.054

MutPred

0.16

Loss of ubiquitination at K211 (P = 0.0603)

MVP

0.30

MPC

0.18

ClinPred

0.16

GERP RS

-4.6

Varity_R

0.12

gMVP

0.077

Mutation Taster

=83/17

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over