rs3136814

Positions:

• chr14-20455138-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The 14-20455138-A-C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0535 in 348,230 control chromosomes in the GnomAD database, including 803 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.065 (480 hom., cov: 33)
  • Exomes 𝑓: 0.045 (323 hom.)
• Consequence: OSGEP ENST00000556439.1 upstream_gene
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.39

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 14-20455138-A-C is Benign according to our data. Variant chr14-20455138-A-C is described in ClinVar as [Benign]. Clinvar id is 1275114.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSGEP	ENST00000556439.1			upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.0650 AC: 9889 AN: 152124 Hom.: 478 Cov.: 33

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0515

Gnomad ASJ AF: 0.0380

Gnomad EAS AF: 0.0162

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.0236

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0393

Gnomad OTH AF: 0.0621

GnomAD4 exome AF: 0.0446 AC: 8741 AN: 195986 Hom.: 323 Cov.: 0 AF XY: 0.0488 AC XY: 5050 AN XY: 103450

Gnomad4 AFR exome AF: 0.116

Gnomad4 AMR exome AF: 0.0493

Gnomad4 ASJ exome AF: 0.0333

Gnomad4 EAS exome AF: 0.0216

Gnomad4 SAS exome AF: 0.0997

Gnomad4 FIN exome AF: 0.0240

Gnomad4 NFE exome AF: 0.0343

Gnomad4 OTH exome AF: 0.0418

GnomAD4 genome AF: 0.0651 AC: 9905 AN: 152244 Hom.: 480 Cov.: 33 AF XY: 0.0643 AC XY: 4788 AN XY: 74434

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.0515

Gnomad4 ASJ AF: 0.0380

Gnomad4 EAS AF: 0.0160

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.0236

Gnomad4 NFE AF: 0.0393

Gnomad4 OTH AF: 0.0614

Alfa AF: 0.0458 Hom.: 204

Bravo AF: 0.0667

Asia WGS AF: 0.0650 AC: 227 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 16, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.32
DANN	Benign	0.59

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3136814; hg19: chr14-20923297;