Variant rs1443735811 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PP5

The NM_017807.4(OSGEP):c.332T>C(p.Ile111Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,461,616 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

OSGEP
NM_017807.4 missense

Scores

Clinical Significance

Pathogenic/Likely pathogenic no assertion criteria provided P:5

Conservation

PhyloP100: 8.76

Variant links:

Genes affected

OSGEP (HGNC:18028): (O-sialoglycoprotein endopeptidase) Predicted to enable N(6)-L-threonylcarbamoyladenine synthase activity and metal ion binding activity. Involved in tRNA threonylcarbamoyladenosine modification. Located in cytoplasm; nuclear speck; and plasma membrane. Part of EKC/KEOPS complex. Implicated in Galloway-Mowat syndrome 3. [provided by Alliance of Genome Resources, Apr 2022]

OSGEP links:

OSGEP (HGNC:):

OSGEP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM1

In a helix (size 12) in uniprot entity OSGEP_HUMAN there are 4 pathogenic changes around while only 0 benign (100%) in NM_017807.4

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 14-20452053-A-G is Pathogenic according to our data. Variant chr14-20452053-A-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 444891.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr14-20452053-A-G is described in Lovd as [Pathogenic]. Variant chr14-20452053-A-G is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSGEP	NM_017807.4 linkuse as main transcript	c.332T>C	p.Ile111Thr	missense_variant	3/11	ENST00000206542.9	NP_060277.1	Q9NPF4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSGEP	ENST00000206542.9 linkuse as main transcript	c.332T>C	p.Ile111Thr	missense_variant	3/11	1	NM_017807.4	ENSP00000206542.4		Q9NPF4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251266

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135788

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1461616

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

727102

show subpopulations

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:

0.0000189

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:5

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not provided

Pathogenic:3

Pathogenic, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Pathogenic, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Likely pathogenic, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -

Galloway-Mowat syndrome 3

Pathogenic:2

Pathogenic, no assertion criteria provided	literature only	OMIM	Oct 26, 2017	- -
Likely pathogenic, no assertion criteria provided	provider interpretation	Solve-RD Consortium	Jun 01, 2022	Variant confirmed as disease-causing by referring clinical team -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.060

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

T;.

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.99

D;D

M_CAP

Benign

0.071

MetaRNN

Uncertain

0.73

D;D

MetaSVM

Uncertain

-0.25

MutationAssessor

Pathogenic

2.9

M;.

PrimateAI

Uncertain

0.58

PROVEAN

Uncertain

-3.7

D;D

REVEL

Uncertain

0.47

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.017

D;.

Polyphen

0.78

P;.

Vest4

0.64

MutPred

0.53

Loss of stability (P = 0.0307);Loss of stability (P = 0.0307);

MVP

0.50

MPC

0.88

ClinPred

0.99

GERP RS

5.6

Varity_R

0.75

gMVP

0.72

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