Variant 16-786047-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_058192.3(RPUSD1):c.842G>A(p.Arg281Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000448 in 1,518,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

RPUSD1
NM_058192.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.370

Variant links:

Genes affected

RPUSD1 (HGNC:14173): (RNA pseudouridine synthase domain containing 1) Predicted to enable pseudouridine synthase activity. Predicted to be involved in enzyme-directed rRNA pseudouridine synthesis. [provided by Alliance of Genome Resources, Apr 2022]

RPUSD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.033795327).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPUSD1	NM_058192.3 linkuse as main transcript	c.842G>A	p.Arg281Gln	missense_variant	6/6	ENST00000007264.7	NP_478072.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPUSD1	ENST00000007264.7 linkuse as main transcript	c.842G>A	p.Arg281Gln	missense_variant	6/6	2	NM_058192.3	ENSP00000007264	P1

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000442

AC:

AN:

158486

Hom.:

AF XY:

0.0000461

AC XY:

AN XY:

86782

show subpopulations

Gnomad AFR exome

AF:

0.0000856

Gnomad AMR exome

AF:

0.0000408

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000546

Gnomad FIN exome

AF:

0.000242

Gnomad NFE exome

AF:

0.0000276

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000359

AC:

AN:

1366118

Hom.:

Cov.:

AF XY:

0.0000418

AC XY:

AN XY:

669820

show subpopulations

Gnomad4 AFR exome

AF:

0.000224

Gnomad4 AMR exome

AF:

0.0000291

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000261

Gnomad4 SAS exome

AF:

0.0000807

Gnomad4 FIN exome

AF:

0.0000524

Gnomad4 NFE exome

AF:

0.0000291

Gnomad4 OTH exome

AF:

0.0000177

GnomAD4 genome

AF:

0.000125

AC:

AN:

152130

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000479

Bravo

AF:

0.0000567

ExAC

AF:

0.0000511

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 31, 2022

The c.842G>A (p.R281Q) alteration is located in exon 6 (coding exon 5) of the RPUSD1 gene. This alteration results from a G to A substitution at nucleotide position 842, causing the arginine (R) at amino acid position 281 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.64

CADD

Benign

1.0

DANN

Benign

0.68

DEOGEN2

Benign

0.011

T;T;T;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.56

.;T;T;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.034

T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.29

N;N;.;.;.

MutationTaster

Benign

1.0

D;N;N;N

PrimateAI

Uncertain

0.54

PROVEAN

Benign

0.26

N;N;N;N;N

REVEL

Benign

0.016

Sift

Benign

0.57

T;T;T;T;T

Sift4G

Benign

0.14

T;T;T;T;T

Polyphen

0.0070

B;B;.;.;.

Vest4

0.16

MutPred

0.13

Loss of methylation at R281 (P = 0.0183);Loss of methylation at R281 (P = 0.0183);.;.;.;

MVP

0.36

MPC

0.092

ClinPred

0.0070

GERP RS

-0.069

Varity_R

0.019

gMVP

0.26

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over