Variant 16-786341-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_058192.3(RPUSD1):c.548T>C(p.Leu183Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,459,484 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

RPUSD1
NM_058192.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.69

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 Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.929

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPUSD1	NM_058192.3 linkuse as main transcript	c.548T>C	p.Leu183Pro	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.548T>C	p.Leu183Pro	missense_variant	6/6	2	NM_058192.3	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000243

AC:

AN:

247226

Hom.:

AF XY:

0.0000223

AC XY:

AN XY:

134596

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000554

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000451

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1459484

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

725884

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000153

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000827

AC:

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

Jun 09, 2022

The c.548T>C (p.L183P) alteration is located in exon 6 (coding exon 5) of the RPUSD1 gene. This alteration results from a T to C substitution at nucleotide position 548, causing the leucine (L) at amino acid position 183 to be replaced by a proline (P). 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

Pathogenic

0.60

BayesDel_addAF

Benign

-0.094

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

T;T;T;.;T

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.040

FATHMM_MKL

Uncertain

0.78

M_CAP

Uncertain

0.14

MetaRNN

Pathogenic

0.93

D;D;D;D;D

MetaSVM

Benign

-0.61

MutationAssessor

Uncertain

2.2

M;M;.;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-4.1

D;D;D;D;D

Sift

Uncertain

0.0030

D;D;D;D;D

Sift4G

Uncertain

0.0040

D;D;D;D;D

Polyphen

0.96

D;D;.;.;.

Vest4

0.53

MutPred

0.87

Loss of stability (P = 0.0156);Loss of stability (P = 0.0156);.;.;.;

MVP

0.34

MPC

0.33

ClinPred

0.73

GERP RS

1.8

Varity_R

0.79

gMVP

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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