Menu
GeneBe

1-201996208-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020216.4(RNPEP):c.799A>G(p.Ile267Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000119 in 1,614,176 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00011 ( 1 hom. )

Consequence

RNPEP
NM_020216.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.93
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]
ELF3-AS1 (HGNC:40211): (ELF3 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.026889533).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RNPEPNM_020216.4 linkuse as main transcriptc.799A>G p.Ile267Val missense_variant 4/11 ENST00000295640.9
RNPEPNM_001319182.2 linkuse as main transcriptc.406A>G p.Ile136Val missense_variant 4/11
RNPEPNM_001319183.2 linkuse as main transcriptc.-218A>G 5_prime_UTR_variant 3/10
RNPEPNM_001319184.2 linkuse as main transcriptc.-72A>G 5_prime_UTR_variant 3/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RNPEPENST00000295640.9 linkuse as main transcriptc.799A>G p.Ile267Val missense_variant 4/111 NM_020216.4 P1
ELF3-AS1ENST00000419190.2 linkuse as main transcriptn.4784T>C non_coding_transcript_exon_variant 2/22

Frequencies

GnomAD3 genomes
AF:
0.000164
AC:
25
AN:
152178
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000135
AC:
34
AN:
251484
Hom.:
0
AF XY:
0.000177
AC XY:
24
AN XY:
135920
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000294
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000193
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000114
AC:
167
AN:
1461880
Hom.:
1
Cov.:
30
AF XY:
0.000128
AC XY:
93
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000359
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000104
Gnomad4 OTH exome
AF:
0.000298
GnomAD4 genome
AF:
0.000164
AC:
25
AN:
152296
Hom.:
0
Cov.:
32
AF XY:
0.000121
AC XY:
9
AN XY:
74470
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000154
Hom.:
0
Bravo
AF:
0.000117
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000465
AC:
4
ExAC
AF:
0.000181
AC:
22
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.000218
EpiControl
AF:
0.000237

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 submitterclinical testingAmbry GeneticsMay 31, 2023The c.799A>G (p.I267V) alteration is located in exon 4 (coding exon 4) of the RNPEP gene. This alteration results from a A to G substitution at nucleotide position 799, causing the isoleucine (I) at amino acid position 267 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
0.075
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.54
Cadd
Benign
14
Dann
Benign
0.84
DEOGEN2
Benign
0.045
T;.;.
Eigen
Benign
-0.77
Eigen_PC
Benign
-0.63
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Benign
0.74
T;T;T
M_CAP
Benign
0.0046
T
MetaRNN
Benign
0.027
T;T;T
MetaSVM
Benign
-0.89
T
MutationAssessor
Benign
-0.075
N;.;.
MutationTaster
Benign
0.99
D;D
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-0.050
N;N;N
REVEL
Benign
0.043
Sift
Benign
0.91
T;T;T
Sift4G
Benign
1.0
T;T;T
Polyphen
0.0
B;.;.
Vest4
0.35
MVP
0.26
MPC
0.14
ClinPred
0.031
T
GERP RS
1.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.013
gMVP
0.37

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.

Other links and lift over

dbSNP: rs201672156; hg19: chr1-201965336; API