Variant 16-786116-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_058192.3(RPUSD1):c.773C>T(p.Pro258Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000246 in 1,598,036 control chromosomes in the GnomAD database, including 5 homozygotes. 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 0.00022 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00025 ( 4 hom. )

Consequence

RPUSD1
NM_058192.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.826

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.

BP4

Computational evidence support a benign effect (MetaRNN=0.07480827).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPUSD1	NM_058192.3 linkuse as main transcript	c.773C>T	p.Pro258Leu	missense_variant	6/6	ENST00000007264.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPUSD1	ENST00000007264.7 linkuse as main transcript	c.773C>T	p.Pro258Leu	missense_variant	6/6	2	NM_058192.3	P1

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000211

AC:

AN:

241860

Hom.:

AF XY:

0.000242

AC XY:

AN XY:

132274

show subpopulations

Gnomad AFR exome

AF:

0.0000660

Gnomad AMR exome

AF:

0.000146

Gnomad ASJ exome

AF:

0.000104

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000397

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000231

Gnomad OTH exome

AF:

0.00118

GnomAD4 exome

AF:

0.000248

AC:

359

AN:

1445716

Hom.:

Cov.:

AF XY:

0.000279

AC XY:

200

AN XY:

716200

show subpopulations

Gnomad4 AFR exome

AF:

0.0000902

Gnomad4 AMR exome

AF:

0.000180

Gnomad4 ASJ exome

AF:

0.0000777

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000431

Gnomad4 FIN exome

AF:

0.0000586

Gnomad4 NFE exome

AF:

0.000174

Gnomad4 OTH exome

AF:

0.000419

GnomAD4 genome

AF:

0.000223

AC:

AN:

152320

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000314

Hom.:

Bravo

AF:

0.000242

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.000583

AC:

ExAC

AF:

0.000224

AC:

Asia WGS

AF:

0.000577

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

Apr 14, 2023

The c.773C>T (p.P258L) alteration is located in exon 6 (coding exon 5) of the RPUSD1 gene. This alteration results from a C to T substitution at nucleotide position 773, causing the proline (P) at amino acid position 258 to be replaced by a leucine (L). 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

0.091

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.50

Cadd

Benign

Dann

Benign

0.96

DEOGEN2

Benign

0.0088

T;T;T;.;T

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.32

M_CAP

Benign

0.026

MetaRNN

Benign

0.075

T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.6

L;L;.;.;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.30

N;N;N;N;N

Sift

Uncertain

0.019

D;D;D;D;D

Sift4G

Uncertain

0.027

D;D;D;D;D

Polyphen

0.0

B;B;.;.;.

Vest4

0.26

MVP

0.17

MPC

0.082

ClinPred

0.022

GERP RS

0.98

Varity_R

0.067

gMVP

0.29

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