Variant 2-189761562-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_022353.3(OSGEPL1):c.79A>C(p.Asn27His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000915 in 1,610,434 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0049 ( 6 hom., cov: 32)

Exomes 𝑓: 0.00050 ( 7 hom. )

Consequence

OSGEPL1
NM_022353.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.267

Variant links:

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]

OSGEPL1 links:

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

ANKAR links:

OSGEPL1 (HGNC:):

OSGEPL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024544).

BP6

Variant 2-189761562-T-G is Benign according to our data. Variant chr2-189761562-T-G is described in ClinVar as [Benign]. Clinvar id is 714135.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00486 (740/152282) while in subpopulation AFR AF= 0.0169 (702/41566). AF 95% confidence interval is 0.0159. There are 6 homozygotes in gnomad4. There are 361 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSGEPL1	NM_022353.3 linkuse as main transcript	c.79A>C	p.Asn27His	missense_variant	2/9	ENST00000264151.10	NP_071748.2	Q9H4B0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSGEPL1	ENST00000264151.10 linkuse as main transcript	c.79A>C	p.Asn27His	missense_variant	2/9	1	NM_022353.3	ENSP00000264151.5		Q9H4B0-1

Frequencies

GnomAD3 genomes

AF:

0.00486

AC:

739

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00138

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00116

AC:

285

AN:

245152

Hom.:

AF XY:

0.000926

AC XY:

123

AN XY:

132890

show subpopulations

Gnomad AFR exome

AF:

0.0167

Gnomad AMR exome

AF:

0.000740

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000344

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000895

Gnomad OTH exome

AF:

0.000335

GnomAD4 exome

AF:

0.000503

AC:

733

AN:

1458152

Hom.:

Cov.:

AF XY:

0.000419

AC XY:

304

AN XY:

725112

show subpopulations

Gnomad4 AFR exome

AF:

0.0188

Gnomad4 AMR exome

AF:

0.000656

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000589

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000900

Gnomad4 OTH exome

AF:

0.000979

GnomAD4 genome

AF:

0.00486

AC:

740

AN:

152282

Hom.:

Cov.:

AF XY:

0.00485

AC XY:

361

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0169

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00124

Hom.:

Bravo

AF:

0.00565

ESP6500AA

AF:

0.0159

AC:

ESP6500EA

AF:

0.000123

AC:

ExAC

AF:

0.00143

AC:

172

Asia WGS

AF:

0.00116

AC:

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 20, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.69

CADD

Benign

1.5

DANN

Benign

0.83

DEOGEN2

Benign

0.013

T;.;T;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.075

LIST_S2

Benign

0.57

.;T;T;T;T

MetaRNN

Benign

0.0025

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;L;L;.;.

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.61

N;N;N;N;N

REVEL

Benign

0.020

Sift

Benign

0.51

T;T;T;T;T

Sift4G

Benign

0.62

T;T;T;.;T

Polyphen

0.0010

B;.;B;.;.

Vest4

0.20

MVP

0.085

MPC

0.14

ClinPred

0.0013

GERP RS

-1.8

Varity_R

0.043

gMVP

0.18

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over