22-30263948-C-G

Variant names:

• chr22-30263948-C-G
• rs971673051
• NM_020530.6:c.694G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020530.6(OSM):​c.694G>C​(p.Val232Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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. V232M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: OSM NM_020530.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06551349).

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.694G>C	p.Val232Leu	missense	Exon 3 of 3	NP_065391.1	P13725
	OSM	NM_001319108.2		c.631G>C	p.Val211Leu	missense	Exon 3 of 3	NP_001306037.1	B5MCX1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSM	ENST00000215781.3	TSL:1 MANE Select	c.694G>C	p.Val232Leu	missense	Exon 3 of 3	ENSP00000215781.2	P13725
	OSM	ENST00000403389.1	TSL:3	c.631G>C	p.Val211Leu	missense	Exon 3 of 3	ENSP00000383893.1	B5MCX1
	OSM	ENST00000403463.1	TSL:3	c.*488G>C		downstream_gene	N/A	ENSP00000384543.1	B5MC70

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.49
DANN	Benign	0.68
DEOGEN2	Benign	0.39	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L
PhyloP100		-1.1
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.014
Sift	Benign	0.34	T
Sift4G	Benign	0.38	T
Polyphen		0.077	B
Vest4		0.065
MutPred		0.11		Loss of methylation at R229 (P = 0.1274)
MVP		0.27
MPC		0.19
ClinPred		0.31	T
GERP RS		-4.8
Varity_R		0.058
gMVP		0.11
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs971673051; hg19: chr22-30659937;