NM_017807.4:c.294A>G

Variant names:

• chr14-20452091-T-C
• rs2275007
• NM_017807.4:c.294A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_017807.4(OSGEP):​c.294A>G​(p.Gln98Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 1,613,168 control chromosomes in the GnomAD database, including 283,945 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (26928 hom., cov: 32)
  • Exomes 𝑓: 0.59 (257017 hom.)
• Consequence: OSGEP NM_017807.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.708
• Publications: 40 publications found

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

ENSG00000258515 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 14-20452091-T-C is Benign according to our data. Variant chr14-20452091-T-C is described in ClinVar as [Benign]. Clinvar id is 1165354.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.708 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSGEP	NM_017807.4	c.294A>G	p.Gln98Gln	synonymous_variant	Exon 3 of 11	ENST00000206542.9	NP_060277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSGEP	ENST00000206542.9	c.294A>G	p.Gln98Gln	synonymous_variant	Exon 3 of 11	1	NM_017807.4	ENSP00000206542.4

Frequencies

GnomAD3 genomes AF: 0.593 AC: 90104 AN: 151878 Hom.: 26887 Cov.: 32

Gnomad AFR AF: 0.607

Gnomad AMI AF: 0.630

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.624

GnomAD2 exomes AF: 0.571 AC: 143294 AN: 250734 AF XY: 0.578

Gnomad AFR exome AF: 0.608

Gnomad AMR exome AF: 0.426

Gnomad ASJ exome AF: 0.653

Gnomad EAS exome AF: 0.428

Gnomad FIN exome AF: 0.687

Gnomad NFE exome AF: 0.601

Gnomad OTH exome AF: 0.604

GnomAD4 exome AF: 0.591 AC: 863424 AN: 1461172 Hom.: 257017 Cov.: 47 AF XY: 0.592 AC XY: 429981 AN XY: 726880

African (AFR) AF: 0.608 AC: 20334 AN: 33470

American (AMR) AF: 0.438 AC: 19589 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.650 AC: 16987 AN: 26114

East Asian (EAS) AF: 0.497 AC: 19741 AN: 39696

South Asian (SAS) AF: 0.576 AC: 49645 AN: 86188

European-Finnish (FIN) AF: 0.677 AC: 36158 AN: 53408

Middle Eastern (MID) AF: 0.639 AC: 3572 AN: 5588

European-Non Finnish (NFE) AF: 0.595 AC: 660994 AN: 1111668

Other (OTH) AF: 0.603 AC: 36404 AN: 60356

GnomAD4 genome AF: 0.594 AC: 90212 AN: 151996 Hom.: 26928 Cov.: 32 AF XY: 0.596 AC XY: 44275 AN XY: 74284

African (AFR) AF: 0.608 AC: 25173 AN: 41414

American (AMR) AF: 0.517 AC: 7891 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 2189 AN: 3470

East Asian (EAS) AF: 0.441 AC: 2279 AN: 5164

South Asian (SAS) AF: 0.566 AC: 2727 AN: 4822

European-Finnish (FIN) AF: 0.689 AC: 7283 AN: 10568

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.597 AC: 40596 AN: 67966

Other (OTH) AF: 0.624 AC: 1316 AN: 2110

Alfa AF: 0.591 Hom.: 118316

Bravo AF: 0.580

Asia WGS AF: 0.541 AC: 1884 AN: 3478

EpiCase AF: 0.599

EpiControl AF: 0.607

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 16, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Galloway-Mowat syndrome 3 Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	4.5
DANN	Benign	0.53
PhyloP100		0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2275007; hg19: chr14-20920250; COSMIC: COSV52832916; COSMIC: COSV52832916;