14-20452681-A-G

Variant names:

• chr14-20452681-A-G
• rs1760945
• NM_017807.4:c.116-233T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_017807.4(OSGEP):​c.116-233T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.937 in 151,414 control chromosomes in the GnomAD database, including 66,489 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.94 (66489 hom., cov: 28)
• Consequence: OSGEP NM_017807.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.470
• Publications: 3 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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 14-20452681-A-G is Benign according to our data. Variant chr14-20452681-A-G is described in ClinVar as Benign. ClinVar VariationId is 1234867.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

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.116-233T>C		intron	N/A	NP_060277.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSGEP	ENST00000206542.9	TSL:1 MANE Select	c.116-233T>C		intron	N/A	ENSP00000206542.4
	OSGEP	ENST00000553640.3	TSL:3	c.116-233T>C		intron	N/A	ENSP00000451580.1
	OSGEP	ENST00000554699.1	TSL:3	n.226-233T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.937 AC: 141698 AN: 151302 Hom.: 66430 Cov.: 28

Gnomad AFR AF: 0.983

Gnomad AMI AF: 0.930

Gnomad AMR AF: 0.889

Gnomad ASJ AF: 0.886

Gnomad EAS AF: 0.951

Gnomad SAS AF: 0.953

Gnomad FIN AF: 0.967

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.915

Gnomad OTH AF: 0.935

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.937 AC: 141814 AN: 151414 Hom.: 66489 Cov.: 28 AF XY: 0.938 AC XY: 69322 AN XY: 73886

African (AFR) AF: 0.983 AC: 40469 AN: 41180

American (AMR) AF: 0.889 AC: 13526 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.886 AC: 3073 AN: 3470

East Asian (EAS) AF: 0.951 AC: 4905 AN: 5156

South Asian (SAS) AF: 0.953 AC: 4599 AN: 4826

European-Finnish (FIN) AF: 0.967 AC: 9938 AN: 10280

Middle Eastern (MID) AF: 0.912 AC: 268 AN: 294

European-Non Finnish (NFE) AF: 0.915 AC: 62228 AN: 67982

Other (OTH) AF: 0.936 AC: 1960 AN: 2094

Alfa AF: 0.942 Hom.: 16937

Bravo AF: 0.930

Asia WGS AF: 0.959 AC: 3337 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 13, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.3
DANN	Benign	0.35
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1760945; hg19: chr14-20920840;