NM_022353.3:c.865G>A

Variant names:

• chr2-189754014-C-T
• rs2045686948
• NM_022353.3:c.865G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_022353.3(OSGEPL1):​c.865G>A​(p.Val289Ile) 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. 14/22 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: OSGEPL1 NM_022353.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.41
• Publications: 0 publications found

Genes affected

OSGEPL1 (HGNC:23075): (O-sialoglycoprotein endopeptidase like 1) Predicted to enable N(6)-L-threonylcarbamoyladenine synthase activity and metal ion binding activity. Predicted to be involved in tRNA threonylcarbamoyladenosine modification. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ANKAR (HGNC:26350): (ankyrin and armadillo repeat containing) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40317017).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022353.3. 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
	OSGEPL1	NM_022353.3	MANE Select	c.865G>A	p.Val289Ile	missense	Exon 5 of 9	NP_071748.2	Q9H4B0-1
	OSGEPL1	NM_001354347.2		c.865G>A	p.Val289Ile	missense	Exon 5 of 9	NP_001341276.2	Q9H4B0-1
	OSGEPL1	NM_001376077.1		c.865G>A	p.Val289Ile	missense	Exon 5 of 9	NP_001363006.1	Q9H4B0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSGEPL1	ENST00000264151.10	TSL:1 MANE Select	c.865G>A	p.Val289Ile	missense	Exon 5 of 9	ENSP00000264151.5	Q9H4B0-1
	OSGEPL1	ENST00000522700.5	TSL:1	c.865G>A	p.Val289Ile	missense	Exon 5 of 8	ENSP00000429697.1	Q9H4B0-1
	OSGEPL1	ENST00000868797.1		c.865G>A	p.Val289Ile	missense	Exon 5 of 9	ENSP00000538856.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Uncertain	0.065	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.010	T
Eigen	Benign	0.037
Eigen_PC	Benign	0.059
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.82	T
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.40	T
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Benign	0.95	L
PhyloP100		1.4
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.23	N
REVEL	Benign	0.14
Sift	Benign	0.40	T
Sift4G	Benign	0.55	T
Polyphen		0.83	P
Vest4		0.18
MutPred		0.68		Loss of MoRF binding (P = 0.1852)
MVP		0.60
MPC		0.11
ClinPred		0.60	D
GERP RS		4.3
Varity_R		0.053
gMVP		0.28
Mutation Taster		=98/2	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: rs2045686948; hg19: chr2-190618740; COSMIC: COSV51462351; COSMIC: COSV51462351;