14-20447274-C-G

Variant names:

Variant summary

Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PM2PM5PP2PP3_Moderate

The NM_017807.4(OSGEP):c.974G>C(p.Arg325Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R325W) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

OSGEP
NM_017807.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.99

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

Galloway-Mowat syndrome 3
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
Galloway-Mowat syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

OSGEP links:

ENSG00000291038 (HGNC:):

ENSG00000291038 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 7 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr14-20447275-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 449687.

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 15 curated pathogenic missense variants (we use a threshold of 10). The gene has 2 curated benign missense variants. Gene score misZ: 0.75927 (below the threshold of 3.09). Trascript score misZ: 1.0429 (below the threshold of 3.09). GenCC associations: The gene is linked to Galloway-Mowat syndrome 3, Galloway-Mowat syndrome.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.853

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017807.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSGEP	NM_017807.4	MANE Select	c.974G>C	p.Arg325Pro	missense	Exon 11 of 11	NP_060277.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
OSGEP	ENST00000206542.9	TSL:1 MANE Select	c.974G>C	p.Arg325Pro	missense	Exon 11 of 11	ENSP00000206542.4
OSGEP	ENST00000553292.1	TSL:2	n.321G>C		non_coding_transcript_exon	Exon 2 of 2
OSGEP	ENST00000554249.5	TSL:2	n.852G>C		non_coding_transcript_exon	Exon 7 of 7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461808

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727216

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111942

Other (OTH)

AF:

0.00

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.33

BayesDel_noAF

Pathogenic

0.24

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.53

Eigen

Pathogenic

0.99

Eigen_PC

Pathogenic

0.92

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Pathogenic

1.0

M_CAP

Uncertain

0.10

MetaRNN

Pathogenic

0.85

MetaSVM

Uncertain

0.10

MutationAssessor

Pathogenic

3.9

PhyloP100

7.0

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-6.7

REVEL

Uncertain

0.51

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.032

Polyphen

1.0

Vest4

0.81

MutPred

0.48

Loss of catalytic residue at R325 (P = 0.0628)

MVP

0.89

MPC

0.44

ClinPred

1.0

GERP RS

5.7

Varity_R

0.96

gMVP

0.95

Mutation Taster

=15/85

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over