chr2-189761529-T-C

Position:

• chr2-189761529-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022353.3(OSGEPL1):​c.112A>G​(p.Ile38Val) 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: OSGEPL1 NM_022353.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.844

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.079144).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OSGEPL1	NM_022353.3	c.112A>G	p.Ile38Val	missense_variant	2/9	ENST00000264151.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OSGEPL1	ENST00000264151.10	c.112A>G	p.Ile38Val	missense_variant	2/9	1	NM_022353.3	P1

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

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 10, 2024

The c.112A>G (p.I38V) alteration is located in exon 2 (coding exon 1) of the OSGEPL1 gene. This alteration results from a A to G substitution at nucleotide position 112, causing the isoleucine (I) at amino acid position 38 to be replaced by a valine (V). 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	0.072
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	8.9
DANN	Benign	0.77
DEOGEN2	Benign	0.013	T;.;T;T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.72	.;T;T;T;T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.079	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;L;L;.;.
MutationTaster	Benign	0.98	N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.36	N;N;N;N;N
REVEL	Benign	0.025
Sift	Benign	0.33	T;T;T;T;T
Sift4G	Benign	0.45	T;T;T;.;T
Polyphen		0.020	B;.;B;.;.
Vest4		0.061
MutPred		0.49		Loss of ubiquitination at K37 (P = 0.0755);Loss of ubiquitination at K37 (P = 0.0755);Loss of ubiquitination at K37 (P = 0.0755);Loss of ubiquitination at K37 (P = 0.0755);Loss of ubiquitination at K37 (P = 0.0755);
MVP		0.092
MPC		0.11
ClinPred		0.097	T
GERP RS		-3.9
Varity_R		0.030
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: chr2-190626255;