NM_017807.4:c.411+90G>A

Variant names:

• chr14-20451884-C-T
• rs1320150
• NM_017807.4:c.411+90G>A

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.411+90G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 1,185,608 control chromosomes in the GnomAD database, including 207,189 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (26667 hom., cov: 33)
  • Exomes 𝑓: 0.59 (180522 hom.)
• Consequence: OSGEP NM_017807.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.31
• 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: Labcorp Genetics (formerly Invitae)
• Galloway-Mowat syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000258515 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 14-20451884-C-T is Benign according to our data. Variant chr14-20451884-C-T is described in ClinVar as Benign. ClinVar VariationId is 1284155.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.592 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.411+90G>A		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.411+90G>A		intron	N/A	ENSP00000206542.4	Q9NPF4
	OSGEP	ENST00000956270.1		c.459+90G>A		intron	N/A	ENSP00000626329.1
	OSGEP	ENST00000883550.1		c.411+90G>A		intron	N/A	ENSP00000553609.1

Frequencies

GnomAD3 genomes AF: 0.590 AC: 89722 AN: 151996 Hom.: 26629 Cov.: 33

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.689

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.622

GnomAD4 exome AF: 0.588 AC: 608155 AN: 1033494 Hom.: 180522 Cov.: 13 AF XY: 0.588 AC XY: 301684 AN XY: 512762

African (AFR) AF: 0.590 AC: 13644 AN: 23128

American (AMR) AF: 0.442 AC: 9796 AN: 22186

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 10828 AN: 16828

East Asian (EAS) AF: 0.499 AC: 17286 AN: 34658

South Asian (SAS) AF: 0.558 AC: 30223 AN: 54184

European-Finnish (FIN) AF: 0.675 AC: 32091 AN: 47562

Middle Eastern (MID) AF: 0.646 AC: 1952 AN: 3020

European-Non Finnish (NFE) AF: 0.592 AC: 465942 AN: 787650

Other (OTH) AF: 0.596 AC: 26393 AN: 44278

GnomAD4 genome AF: 0.591 AC: 89826 AN: 152114 Hom.: 26667 Cov.: 33 AF XY: 0.593 AC XY: 44117 AN XY: 74366

African (AFR) AF: 0.598 AC: 24811 AN: 41484

American (AMR) AF: 0.516 AC: 7880 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 2189 AN: 3468

East Asian (EAS) AF: 0.441 AC: 2281 AN: 5170

South Asian (SAS) AF: 0.565 AC: 2727 AN: 4828

European-Finnish (FIN) AF: 0.689 AC: 7292 AN: 10578

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.597 AC: 40576 AN: 67984

Other (OTH) AF: 0.622 AC: 1313 AN: 2112

Alfa AF: 0.586 Hom.: 3392

Bravo AF: 0.577

Asia WGS AF: 0.540 AC: 1881 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.3
DANN	Benign	0.79
PhyloP100		-1.3
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: rs1320150; hg19: chr14-20920043;