2-189754014-C-T

Position:

• chr2-189754014-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. 13/21 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: OSGEPL1 NM_022353.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.41

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OSGEPL1	NM_022353.3	c.865G>A	p.Val289Ile	missense_variant	5/9	ENST00000264151.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OSGEPL1	ENST00000264151.10	c.865G>A	p.Val289Ile	missense_variant	5/9	1	NM_022353.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2023

The c.865G>A (p.V289I) alteration is located in exon 5 (coding exon 4) of the OSGEPL1 gene. This alteration results from a G to A substitution at nucleotide position 865, causing the valine (V) at amino acid position 289 to be replaced by an isoleucine (I). 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	0.090
BayesDel_addAF	Uncertain	0.065	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.010	T;.;T;.
Eigen	Benign	0.037
Eigen_PC	Benign	0.059
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.82	.;T;T;T
M_CAP	Uncertain	0.23	D
MetaRNN	Benign	0.40	T;T;T;T
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Benign	0.95	L;L;L;.
MutationTaster	Benign	0.84	D;D
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.23	N;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.40	T;T;T;T
Sift4G	Benign	0.55	T;T;T;T
Polyphen		0.83	P;.;P;.
Vest4		0.18
MutPred		0.68		Loss of MoRF binding (P = 0.1852);Loss of MoRF binding (P = 0.1852);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

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: chr2-190618740; COSMIC: COSV51462351; COSMIC: COSV51462351;