chr5-38869072-A-G

Position:

• chr5-38869072-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003999.3(OSMR):​c.28A>G​(p.Thr10Ala) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OSMR NM_003999.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.640

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06432068).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSMR	NM_003999.3	c.28A>G	p.Thr10Ala	missense_variant	2/18	ENST00000274276.8	NP_003990.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSMR	ENST00000274276.8	c.28A>G	p.Thr10Ala	missense_variant	2/18	1	NM_003999.3	ENSP00000274276	P1
OSMR	ENST00000502536.5	c.28A>G	p.Thr10Ala	missense_variant	2/7	1		ENSP00000422023

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 02, 2023

The c.28A>G (p.T10A) alteration is located in exon 2 (coding exon 1) of the OSMR gene. This alteration results from a A to G substitution at nucleotide position 28, causing the threonine (T) at amino acid position 10 to be replaced by an alanine (A). 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	0.057
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.13
DANN	Benign	0.43
DEOGEN2	Benign	0.082	.;T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.45	T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.064	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.99	N;N
REVEL	Benign	0.041
Sift	Benign	0.43	T;T
Sift4G	Benign	0.43	T;T
Polyphen		0.21	B;B
Vest4		0.071
MutPred		0.38		Loss of phosphorylation at T10 (P = 0.2549);Loss of phosphorylation at T10 (P = 0.2549);
MVP		0.50
MPC		0.084
ClinPred		0.13	T
GERP RS		0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.042
gMVP		0.38

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-38869174; COSMIC: COSV57091926;