chr2-189754302-G-T

Position:

• chr2-189754302-G-T

Variant summary

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

The NM_022353.3(OSGEPL1):​c.653C>A​(p.Thr218Asn) 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: 1.36

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 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=0.06253582).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OSGEPL1	NM_022353.3	c.653C>A	p.Thr218Asn	missense_variant	4/9	ENST00000264151.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OSGEPL1	ENST00000264151.10	c.653C>A	p.Thr218Asn	missense_variant	4/9	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

Mar 16, 2022

The c.653C>A (p.T218N) alteration is located in exon 4 (coding exon 3) of the OSGEPL1 gene. This alteration results from a C to A substitution at nucleotide position 653, causing the threonine (T) at amino acid position 218 to be replaced by an asparagine (N). 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	0.088
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	15
DANN	Benign	0.84
DEOGEN2	Benign	0.0048	T;.;T;.;T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.85	.;T;D;D;D
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.063	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.98	L;L;L;.;.
MutationTaster	Benign	0.67	N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.090	N;N;N;N;N
REVEL	Benign	0.032
Sift	Benign	0.56	T;T;T;T;T
Sift4G	Benign	0.52	T;T;T;T;.
Polyphen		0.23	B;.;B;.;.
Vest4		0.11
MutPred		0.55		Loss of methylation at K223 (P = 0.1272);Loss of methylation at K223 (P = 0.1272);Loss of methylation at K223 (P = 0.1272);.;Loss of methylation at K223 (P = 0.1272);
MVP		0.19
MPC		0.16
ClinPred		0.097	T
GERP RS		2.5
Varity_R		0.034
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr2-190619028;