2-189754312-C-G

Variant names:

• chr2-189754312-C-G
• NM_022353.3:c.643G>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.643G>C​(p.Glu215Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: OSGEPL1 NM_022353.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.61

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18121752).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSGEPL1	NM_022353.3	c.643G>C	p.Glu215Gln	missense_variant	Exon 4 of 9	ENST00000264151.10	NP_071748.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSGEPL1	ENST00000264151.10	c.643G>C	p.Glu215Gln	missense_variant	Exon 4 of 9	1	NM_022353.3	ENSP00000264151.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1458878 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725314

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000546

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.643G>C (p.E215Q) alteration is located in exon 4 (coding exon 3) of the OSGEPL1 gene. This alteration results from a G to C substitution at nucleotide position 643, causing the glutamic acid (E) at amino acid position 215 to be replaced by a glutamine (Q). 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	0.080
BayesDel_addAF	Uncertain	0.024	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.021	T;.;T;.;T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.084
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.87	.;D;D;D;D
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.18	T;T;T;T;T
MetaSVM	Uncertain	0.54	D
MutationAssessor	Benign	1.1	L;L;L;.;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.9	N;N;N;N;N
REVEL	Benign	0.097
Sift	Benign	0.14	T;T;T;T;T
Sift4G	Benign	0.28	T;T;T;T;.
Polyphen		0.0040	B;.;B;.;.
Vest4		0.11
MutPred		0.35		Loss of ubiquitination at K212 (P = 0.0901);Loss of ubiquitination at K212 (P = 0.0901);Loss of ubiquitination at K212 (P = 0.0901);.;Loss of ubiquitination at K212 (P = 0.0901);
MVP		0.58
MPC		0.15
ClinPred		0.31	T
GERP RS		5.3
Varity_R		0.13
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: chr2-190619038;