rs3120073

chr14-20448546-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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/exons	MANE	UniProt
OSGEP	NM_017807.4	c.636+187A>G		intron_variant		ENST00000206542.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OSGEP	ENST00000206542.9	c.636+187A>G		intron_variant		1	NM_017807.4	P1

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

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.170

Gnomad4 EAS AF: 0.0699

Gnomad4 SAS AF: 0.0649

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.241

Alfa AF: 0.245 Hom.: 4325

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 13, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	4.1
Dann	Benign	0.68

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: rs3120073; hg19: chr14-20916705;