Genetic Variant RPUSD2:p.Pro113Ser (chr15-40569674-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_152260.3(RPUSD2):c.337C>T(p.Pro113Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000172 in 1,556,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

RPUSD2
NM_152260.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.03

Publications

0 publications found

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]

RPUSD2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1395225).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152260.3. 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
	RPUSD2	NM_152260.3	MANE Select	c.337C>T	p.Pro113Ser	missense	Exon 1 of 3	NP_689473.1	Q8IZ73-1
	RPUSD2	NM_001286407.2		c.337C>T	p.Pro113Ser	missense	Exon 1 of 3	NP_001273336.1	Q8IZ73-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPUSD2	ENST00000315616.12	TSL:1 MANE Select	c.337C>T	p.Pro113Ser	missense	Exon 1 of 3	ENSP00000323288.7	Q8IZ73-1
RPUSD2	ENST00000917964.1		c.337C>T	p.Pro113Ser	missense	Exon 1 of 3	ENSP00000588023.1
RPUSD2	ENST00000559271.1	TSL:2	c.337C>T	p.Pro113Ser	missense	Exon 1 of 3	ENSP00000453036.1	Q8IZ73-2

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000138

AC:

AN:

173640

AF XY:

0.000194

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000382

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000193

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000174

AC:

244

AN:

1404264

Hom.:

Cov.:

AF XY:

0.000193

AC XY:

134

AN XY:

692520

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32492

American (AMR)

AF:

0.000243

AC:

AN:

37054

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24112

East Asian (EAS)

AF:

0.00

AC:

AN:

37560

South Asian (SAS)

AF:

0.00

AC:

AN:

79182

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49290

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5644

European-Non Finnish (NFE)

AF:

0.000213

AC:

230

AN:

1080808

Other (OTH)

AF:

0.0000860

AC:

AN:

58122

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000158

AC:

AN:

152332

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41582

American (AMR)

AF:

0.000327

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000265

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000150

Hom.:

Bravo

AF:

0.000110

ExAC

AF:

0.0000584

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.092

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.044

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.6

PhyloP100

7.0

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-1.6

REVEL

Benign

0.18

Sift

Uncertain

0.010

Sift4G

Uncertain

0.010

Polyphen

0.99

Vest4

0.39

MVP

0.79

MPC

0.87

ClinPred

0.45

GERP RS

4.5

PromoterAI

0.013

Neutral

(source)

Varity_R

0.15

gMVP

0.60

Mutation Taster

=83/17

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over