rs3120073

Variant names:

• chr14-20448546-T-C
• rs3120073
• NM_017807.4:c.636+187A>G

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.636+187A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 152,060 control chromosomes in the GnomAD database, including 4,240 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.23 (4240 hom., cov: 32)
• Consequence: OSGEP NM_017807.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0980
• Publications: 15 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=-0.85).
• BP6: Variant 14-20448546-T-C is Benign according to our data. Variant chr14-20448546-T-C is described in ClinVar as [Benign]. Clinvar id is 1285732.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSGEP	NM_017807.4	c.636+187A>G		intron_variant	Intron 6 of 10	ENST00000206542.9	NP_060277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSGEP	ENST00000206542.9	c.636+187A>G		intron_variant	Intron 6 of 10	1	NM_017807.4	ENSP00000206542.4

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35105 AN: 151942 Hom.: 4236 Cov.: 32

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.0700

Gnomad SAS AF: 0.0644

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.231 AC: 35159 AN: 152060 Hom.: 4240 Cov.: 32 AF XY: 0.231 AC XY: 17157 AN XY: 74340

African (AFR) AF: 0.211 AC: 8740 AN: 41478

American (AMR) AF: 0.224 AC: 3419 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 590 AN: 3470

East Asian (EAS) AF: 0.0699 AC: 362 AN: 5176

South Asian (SAS) AF: 0.0649 AC: 313 AN: 4826

European-Finnish (FIN) AF: 0.306 AC: 3236 AN: 10564

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.261 AC: 17767 AN: 67972

Other (OTH) AF: 0.241 AC: 507 AN: 2108

Alfa AF: 0.244 Hom.: 5724

Bravo AF: 0.227

Asia WGS AF: 0.0970 AC: 340 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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.1
DANN	Benign	0.68
PhyloP100		-0.098
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: rs3120073; hg19: chr14-20916705;