Variant chr1-201996182-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_020216.4(RNPEP):c.773C>T(p.Ala258Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,180 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

RNPEP
NM_020216.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.29

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:

ELF3-AS1 (HGNC:40211): (ELF3 antisense RNA 1)

ELF3-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2703247).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RNPEP	NM_020216.4 linkuse as main transcript	c.773C>T	p.Ala258Val	missense_variant	4/11	ENST00000295640.9	NP_064601.3
RNPEP	NM_001319182.2 linkuse as main transcript	c.380C>T	p.Ala127Val	missense_variant	4/11		NP_001306111.1
RNPEP	NM_001319183.2 linkuse as main transcript	c.-244C>T		5_prime_UTR_variant	3/10		NP_001306112.1
RNPEP	NM_001319184.2 linkuse as main transcript	c.-98C>T		5_prime_UTR_variant	3/10		NP_001306113.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNPEP	ENST00000295640.9 linkuse as main transcript	c.773C>T	p.Ala258Val	missense_variant	4/11	1	NM_020216.4	ENSP00000295640	P1
ELF3-AS1	ENST00000419190.2 linkuse as main transcript	n.4810G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.00000756

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 17, 2024

The c.773C>T (p.A258V) alteration is located in exon 4 (coding exon 4) of the RNPEP gene. This alteration results from a C to T substitution at nucleotide position 773, causing the alanine (A) at amino acid position 258 to be replaced by a valine (V). 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

0.11

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

T;.;.

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.66

LIST_S2

Uncertain

0.87

D;D;D

M_CAP

Benign

0.015

MetaRNN

Benign

0.27

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

M;.;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-2.1

N;N;N

REVEL

Benign

0.13

Sift

Benign

0.47

T;T;D

Sift4G

Benign

0.075

T;T;D

Polyphen

0.95

P;.;.

Vest4

0.58

MutPred

0.54

Loss of ubiquitination at K260 (P = 0.0863);.;.;

MVP

0.42

MPC

0.32

ClinPred

0.39

GERP RS

3.4

Varity_R

0.020

gMVP

0.61

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

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