Variant chr1-201982847-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The ENST00000295640.9(RNPEP):c.181G>T(p.Gly61Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000037 in 1,350,116 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: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000033 ( 0 hom. )

Consequence

RNPEP
ENST00000295640.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.80

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 Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.949

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RNPEP	NM_020216.4 linkuse as main transcript	c.181G>T	p.Gly61Cys	missense_variant	1/11	ENST00000295640.9	NP_064601.3
RNPEP	NM_001319183.2 linkuse as main transcript	c.-687G>T		5_prime_UTR_variant	1/10		NP_001306112.1
RNPEP	NM_001319184.2 linkuse as main transcript	c.-541G>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.181G>T	p.Gly61Cys	missense_variant	1/11	1	NM_020216.4	ENSP00000295640	P1

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151784

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000334

AC:

AN:

1198332

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

580788

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000304

Gnomad4 OTH exome

AF:

0.0000205

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151784

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74160

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

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

Jan 31, 2022

The c.181G>T (p.G61C) 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 181, causing the glycine (G) at amino acid position 61 to be replaced by a cysteine (C). 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

0.90

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.10

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

T;.

Eigen

Uncertain

0.32

Eigen_PC

Benign

0.10

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.77

T;T

M_CAP

Pathogenic

0.33

MetaRNN

Pathogenic

0.95

D;D

MetaSVM

Benign

-0.87

MutationAssessor

Pathogenic

3.7

H;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-4.2

D;D

REVEL

Uncertain

0.40

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

1.0

D;.

Vest4

0.59

MutPred

0.83

Loss of glycosylation at S60 (P = 0.0506);Loss of glycosylation at S60 (P = 0.0506);

MVP

0.56

MPC

0.68

ClinPred

1.0

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.74

gMVP

0.69

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