15-40571713-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_152260.3(RPUSD2):​c.716C>T​(p.Ser239Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,892 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: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RPUSD2
NM_152260.3 missense

Scores

5
9
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.71
Variant links:
Genes affected
RPUSD2 (HGNC:24180): (RNA pseudouridine synthase domain containing 2) Enables pseudouridine synthase activity. Involved in mRNA pseudouridine synthesis. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.795

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RPUSD2NM_152260.3 linkc.716C>T p.Ser239Phe missense_variant Exon 2 of 3 ENST00000315616.12 NP_689473.1 Q8IZ73-1
RPUSD2NM_001286407.2 linkc.533C>T p.Ser178Phe missense_variant Exon 2 of 3 NP_001273336.1 Q8IZ73-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RPUSD2ENST00000315616.12 linkc.716C>T p.Ser239Phe missense_variant Exon 2 of 3 1 NM_152260.3 ENSP00000323288.7 Q8IZ73-1
RPUSD2ENST00000559271.1 linkc.533C>T p.Ser178Phe missense_variant Exon 2 of 3 2 ENSP00000453036.1 Q8IZ73-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461892
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Sep 13, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.716C>T (p.S239F) alteration is located in exon 2 (coding exon 2) of the RPUSD2 gene. This alteration results from a C to T substitution at nucleotide position 716, causing the serine (S) at amino acid position 239 to be replaced by a phenylalanine (F). 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
0.82
BayesDel_addAF
Uncertain
0.073
D
BayesDel_noAF
Benign
-0.13
CADD
Pathogenic
30
DANN
Uncertain
1.0
DEOGEN2
Benign
0.16
T;.
Eigen
Pathogenic
0.87
Eigen_PC
Pathogenic
0.86
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.96
D;D
M_CAP
Benign
0.018
T
MetaRNN
Pathogenic
0.79
D;D
MetaSVM
Benign
-0.99
T
MutationAssessor
Uncertain
2.1
M;.
PrimateAI
Uncertain
0.53
T
PROVEAN
Uncertain
-3.7
D;D
REVEL
Uncertain
0.40
Sift
Uncertain
0.0020
D;D
Sift4G
Uncertain
0.0020
D;D
Polyphen
1.0
D;.
Vest4
0.80
MutPred
0.54
Gain of catalytic residue at S239 (P = 0.0026);.;
MVP
0.65
MPC
0.91
ClinPred
0.98
D
GERP RS
5.8
Varity_R
0.93
gMVP
0.78

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.

Other links and lift over

dbSNP: rs1891143233; hg19: chr15-40863912; COSMIC: COSV59766495; COSMIC: COSV59766495; API