rs1443735811

chr14-20452053-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

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
• Clinical Significance: Pathogenic/Likely pathogenic no assertion criteria provided P:4
• Conservation: PhyloP100: 8.76

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• 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	UniProt
OSGEP	NM_017807.4	c.332T>C	p.Ile111Thr	missense_variant	3/11	ENST00000206542.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OSGEP	ENST00000206542.9	c.332T>C	p.Ile111Thr	missense_variant	3/11	1	NM_017807.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000796 AC: 2 AN: 251266 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135788

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: 21 AN: 1461616 Hom.: 0 Cov.: 31 AF XY: 0.0000206 AC XY: 15 AN XY: 727102

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.: 33

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:4

Revision: no assertion criteria provided

Submissions by phenotype

not provided Pathogenic:3

Likely pathogenic, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
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	-	- -

Galloway-Mowat syndrome 3 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Oct 26, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.060
Cadd	Pathogenic	26
Dann	Uncertain	1.0
DEOGEN2	Benign	0.32	T;.
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D;D
M_CAP	Benign	0.071	D
MetaRNN	Uncertain	0.73	D;D
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Pathogenic	2.9	M;.
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.58	T
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	D
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

Other links and lift over

dbSNP: rs1443735811; hg19: chr14-20920212;