Variant 1-201982956-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_020216.4(RNPEP):c.290G>T(p.Arg97Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00257 in 1,492,954 control chromosomes in the GnomAD database, including 13 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 0.0019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 13 hom. )

Consequence

RNPEP
NM_020216.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.916

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 made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006571859).

BS2

High Homozygotes in GnomAdExome4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RNPEP	NM_020216.4 linkuse as main transcript	c.290G>T	p.Arg97Leu	missense_variant	1/11	ENST00000295640.9	NP_064601.3
RNPEP	NM_001319183.2 linkuse as main transcript	c.-578G>T		5_prime_UTR_variant	1/10		NP_001306112.1
RNPEP	NM_001319184.2 linkuse as main transcript	c.-432G>T		5_prime_UTR_variant	1/10		NP_001306113.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNPEP	ENST00000295640.9 linkuse as main transcript	c.290G>T	p.Arg97Leu	missense_variant	1/11	1	NM_020216.4	ENSP00000295640	P1

Frequencies

GnomAD3 genomes

AF:

0.00186

AC:

282

AN:

151956

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000700

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00282

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00281

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00154

AC:

132

AN:

85534

Hom.:

AF XY:

0.00167

AC XY:

AN XY:

48422

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00190

Gnomad ASJ exome

AF:

0.000157

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000597

Gnomad FIN exome

AF:

0.000810

Gnomad NFE exome

AF:

0.00273

Gnomad OTH exome

AF:

0.00172

GnomAD4 exome

AF:

0.00265

AC:

3549

AN:

1340890

Hom.:

Cov.:

AF XY:

0.00261

AC XY:

1724

AN XY:

660934

show subpopulations

Gnomad4 AFR exome

AF:

0.000482

Gnomad4 AMR exome

AF:

0.00161

Gnomad4 ASJ exome

AF:

0.000214

Gnomad4 EAS exome

AF:

0.0000345

Gnomad4 SAS exome

AF:

0.000679

Gnomad4 FIN exome

AF:

0.00105

Gnomad4 NFE exome

AF:

0.00311

Gnomad4 OTH exome

AF:

0.00177

GnomAD4 genome

AF:

0.00185

AC:

282

AN:

152064

Hom.:

Cov.:

AF XY:

0.00161

AC XY:

120

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.000698

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00281

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00118

Hom.:

Bravo

AF:

0.00182

ExAC

AF:

0.000293

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 18, 2021

The c.290G>T (p.R97L) alteration is located in exon 1 (coding exon 1) of the RNPEP gene. This alteration results from a G to T substitution at nucleotide position 290, causing the arginine (R) at amino acid position 97 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

0.069

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.79

DANN

Benign

0.91

DEOGEN2

Benign

0.044

T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.061

LIST_S2

Benign

0.47

T;T

M_CAP

Benign

0.069

MetaRNN

Benign

0.0066

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-0.20

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.050

N;N

REVEL

Benign

0.0080

Sift

Benign

0.28

T;T

Sift4G

Benign

0.31

T;T

Polyphen

0.0

B;.

Vest4

0.072

MVP

0.21

MPC

0.19

ClinPred

0.017

GERP RS

-2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.054

gMVP

0.35

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