Menu
GeneBe

1-201996202-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020216.4(RNPEP):c.793G>A(p.Gly265Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,614,044 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

RNPEP
NM_020216.4 missense

Scores

2
12
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.06
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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RNPEPNM_020216.4 linkuse as main transcriptc.793G>A p.Gly265Arg missense_variant 4/11 ENST00000295640.9
RNPEPNM_001319182.2 linkuse as main transcriptc.400G>A p.Gly134Arg missense_variant 4/11
RNPEPNM_001319183.2 linkuse as main transcriptc.-224G>A 5_prime_UTR_variant 3/10
RNPEPNM_001319184.2 linkuse as main transcriptc.-78G>A 5_prime_UTR_variant 3/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RNPEPENST00000295640.9 linkuse as main transcriptc.793G>A p.Gly265Arg missense_variant 4/111 NM_020216.4 P1
ELF3-AS1ENST00000419190.2 linkuse as main transcriptn.4790C>T non_coding_transcript_exon_variant 2/22

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152168
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461876
Hom.:
0
Cov.:
30
AF XY:
0.00000275
AC XY:
2
AN XY:
727234
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:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152168
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74322
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000147
Gnomad4 OTH
AF:
0.00

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 GeneticsJun 29, 2023The c.793G>A (p.G265R) alteration is located in exon 4 (coding exon 4) of the RNPEP gene. This alteration results from a G to A substitution at nucleotide position 793, causing the glycine (G) at amino acid position 265 to be replaced by an arginine (R). 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
0.33
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
-0.020
Cadd
Pathogenic
26
Dann
Pathogenic
1.0
DEOGEN2
Benign
0.26
T;.;.
Eigen
Uncertain
0.55
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.94
D;D;D
M_CAP
Benign
0.032
D
MetaRNN
Uncertain
0.62
D;D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.2
M;.;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.50
T
PROVEAN
Pathogenic
-4.6
D;D;D
REVEL
Uncertain
0.32
Sift
Uncertain
0.0080
D;D;T
Sift4G
Uncertain
0.034
D;D;T
Polyphen
1.0
D;.;.
Vest4
0.61
MutPred
0.52
Gain of solvent accessibility (P = 0.0674);.;.;
MVP
0.58
MPC
0.72
ClinPred
0.97
D
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.39
gMVP
0.77

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs1683542851; hg19: chr1-201965330; API