chr14-20448090-T-C

Variant names:

• chr14-20448090-T-C
• rs2275008
• NM_017807.4:c.702+16A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017807.4(OSGEP):​c.702+16A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 1,607,860 control chromosomes in the GnomAD database, including 68,291 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (6800 hom., cov: 32)
  • Exomes 𝑓: 0.28 (61491 hom.)
• Consequence: OSGEP NM_017807.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.947
• Publications: 28 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: Labcorp Genetics (formerly Invitae), PanelApp Australia
• Galloway-Mowat syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 14-20448090-T-C is Benign according to our data. Variant chr14-20448090-T-C is described in ClinVar as Benign. ClinVar VariationId is 1165073.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.337 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSGEP	NM_017807.4	MANE Select	c.702+16A>G		intron	N/A	NP_060277.1	Q9NPF4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSGEP	ENST00000206542.9	TSL:1 MANE Select	c.702+16A>G		intron	N/A	ENSP00000206542.4	Q9NPF4
	OSGEP	ENST00000956270.1		c.750+16A>G		intron	N/A	ENSP00000626329.1
	OSGEP	ENST00000883550.1		c.702+16A>G		intron	N/A	ENSP00000553609.1

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44788 AN: 151882 Hom.: 6792 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.0860

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.297

GnomAD2 exomes AF: 0.256 AC: 64436 AN: 251336 AF XY: 0.252

Gnomad AFR exome AF: 0.338

Gnomad AMR exome AF: 0.238

Gnomad ASJ exome AF: 0.206

Gnomad EAS exome AF: 0.0789

Gnomad FIN exome AF: 0.331

Gnomad NFE exome AF: 0.294

Gnomad OTH exome AF: 0.269

GnomAD4 exome AF: 0.285 AC: 414876 AN: 1455858 Hom.: 61491 Cov.: 29 AF XY: 0.281 AC XY: 203354 AN XY: 724686

African (AFR) AF: 0.338 AC: 11292 AN: 33362

American (AMR) AF: 0.240 AC: 10740 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 5369 AN: 26104

East Asian (EAS) AF: 0.108 AC: 4278 AN: 39680

South Asian (SAS) AF: 0.164 AC: 14169 AN: 86154

European-Finnish (FIN) AF: 0.326 AC: 17391 AN: 53410

Middle Eastern (MID) AF: 0.200 AC: 1153 AN: 5758

European-Non Finnish (NFE) AF: 0.302 AC: 334084 AN: 1106462

Other (OTH) AF: 0.272 AC: 16400 AN: 60210

GnomAD4 genome AF: 0.295 AC: 44862 AN: 152002 Hom.: 6800 Cov.: 32 AF XY: 0.294 AC XY: 21834 AN XY: 74284

African (AFR) AF: 0.342 AC: 14160 AN: 41448

American (AMR) AF: 0.263 AC: 4010 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 707 AN: 3472

East Asian (EAS) AF: 0.0858 AC: 444 AN: 5174

South Asian (SAS) AF: 0.161 AC: 773 AN: 4814

European-Finnish (FIN) AF: 0.331 AC: 3494 AN: 10562

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.300 AC: 20368 AN: 67954

Other (OTH) AF: 0.296 AC: 623 AN: 2104

Alfa AF: 0.284 Hom.: 14294

Bravo AF: 0.292

Asia WGS AF: 0.155 AC: 540 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.86
DANN	Benign	0.62
PhyloP100		-0.95
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		2.0
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: rs2275008; hg19: chr14-20916249; COSMIC: COSV52831608; COSMIC: COSV52831608;