dbSNP rs201819747: RNPEP:p.Ser125Phe (chr1-201983040-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_020216.4(RNPEP):c.374C>T(p.Ser125Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000996 in 1,528,062 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 2 hom. )

Consequence

RNPEP
NM_020216.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.976

Publications

3 publications found

Variant links:

Genes affected

RNPEP (HGNC:10078): (arginyl aminopeptidase) Predicted to enable metalloaminopeptidase activity. Predicted to be involved in proteolysis. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

RNPEP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012843728).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020216.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
RNPEP	NM_020216.4	MANE Select	c.374C>T	p.Ser125Phe	missense	Exon 1 of 11	NP_064601.3
RNPEP	NM_001319183.2		c.-494C>T		5_prime_UTR	Exon 1 of 10	NP_001306112.1
RNPEP	NM_001319184.2		c.-348C>T		5_prime_UTR	Exon 1 of 10	NP_001306113.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RNPEP	ENST00000295640.9	TSL:1 MANE Select	c.374C>T	p.Ser125Phe	missense	Exon 1 of 11	ENSP00000295640.4	Q9H4A4
RNPEP	ENST00000471105.5	TSL:1	n.86C>T		non_coding_transcript_exon	Exon 1 of 10
RNPEP	ENST00000967255.1		c.374C>T	p.Ser125Phe	missense	Exon 1 of 11	ENSP00000637314.1

Frequencies

GnomAD3 genomes

AF:

0.000506

AC:

AN:

152082

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000956

Gnomad OTH

AF:

0.000959

GnomAD2 exomes

AF:

0.000453

AC:

AN:

121364

AF XY:

0.000457

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000919

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000773

Gnomad NFE exome

AF:

0.00109

Gnomad OTH exome

AF:

0.000868

GnomAD4 exome

AF:

0.00105

AC:

1445

AN:

1375980

Hom.:

Cov.:

AF XY:

0.000976

AC XY:

664

AN XY:

680012

show subpopulations

African (AFR)

AF:

0.000140

AC:

AN:

28574

American (AMR)

AF:

0.000120

AC:

AN:

33406

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24204

East Asian (EAS)

AF:

0.00

AC:

AN:

32284

South Asian (SAS)

AF:

0.0000129

AC:

AN:

77522

European-Finnish (FIN)

AF:

0.0000884

AC:

AN:

45230

Middle Eastern (MID)

AF:

0.000829

AC:

AN:

4826

European-Non Finnish (NFE)

AF:

0.00130

AC:

1391

AN:

1072990

Other (OTH)

AF:

0.000650

AC:

AN:

56944

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

171

256

342

427

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

168

224

280

<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:

0.000506

AC:

AN:

152082

Hom.:

Cov.:

AF XY:

0.000350

AC XY:

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.000217

AC:

AN:

41424

American (AMR)

AF:

0.0000655

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000956

AC:

AN:

67970

Other (OTH)

AF:

0.000959

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

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:

0.000408

Hom.:

Bravo

AF:

0.000612

ExAC

AF:

0.000235

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

0.13

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

Eigen

Benign

-0.96

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.68

M_CAP

Benign

0.016

MetaRNN

Benign

0.013

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

PhyloP100

-0.98

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.057

Sift

Benign

0.033

Sift4G

Uncertain

0.035

Polyphen

0.54

Vest4

0.12

MVP

0.19

MPC

0.17

ClinPred

0.15

GERP RS

-5.5

PromoterAI

-0.0022

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.12

gMVP

0.32

Mutation Taster

=97/3

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