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GeneBe

1-201997524-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020216.4(RNPEP):c.1060G>A(p.Ala354Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00019 in 1,613,836 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00034 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00018 ( 1 hom. )

Consequence

RNPEP
NM_020216.4 missense

Scores

3
6
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.36
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.14988992).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RNPEPNM_020216.4 linkuse as main transcriptc.1060G>A p.Ala354Thr missense_variant 5/11 ENST00000295640.9
RNPEPNM_001319182.2 linkuse as main transcriptc.667G>A p.Ala223Thr missense_variant 5/11
RNPEPNM_001319183.2 linkuse as main transcriptc.190G>A p.Ala64Thr missense_variant 4/10
RNPEPNM_001319184.2 linkuse as main transcriptc.190G>A p.Ala64Thr missense_variant 4/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RNPEPENST00000295640.9 linkuse as main transcriptc.1060G>A p.Ala354Thr missense_variant 5/111 NM_020216.4 P1
ELF3-AS1ENST00000419190.2 linkuse as main transcriptn.3468C>T non_coding_transcript_exon_variant 2/22

Frequencies

GnomAD3 genomes
AF:
0.000335
AC:
51
AN:
152104
Hom.:
0
Cov.:
31
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:
0.00151
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000500
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000255
AC:
64
AN:
251446
Hom.:
0
AF XY:
0.000199
AC XY:
27
AN XY:
135894
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000578
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00125
Gnomad NFE exome
AF:
0.000281
Gnomad OTH exome
AF:
0.000489
GnomAD4 exome
AF:
0.000175
AC:
256
AN:
1461732
Hom.:
1
Cov.:
31
AF XY:
0.000183
AC XY:
133
AN XY:
727142
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00129
Gnomad4 NFE exome
AF:
0.000156
Gnomad4 OTH exome
AF:
0.000132
GnomAD4 genome
AF:
0.000335
AC:
51
AN:
152104
Hom.:
0
Cov.:
31
AF XY:
0.000269
AC XY:
20
AN XY:
74290
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:
0.00151
Gnomad4 NFE
AF:
0.000500
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.000252
Hom.:
1
Bravo
AF:
0.000106
ExAC
AF:
0.000321
AC:
39
EpiCase
AF:
0.000218
EpiControl
AF:
0.000296

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 GeneticsApr 04, 2023The c.1060G>A (p.A354T) alteration is located in exon 5 (coding exon 5) of the RNPEP gene. This alteration results from a G to A substitution at nucleotide position 1060, causing the alanine (A) at amino acid position 354 to be replaced by a threonine (T). 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
Uncertain
0.52
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.13
Cadd
Pathogenic
32
Dann
Uncertain
1.0
DEOGEN2
Benign
0.13
T;.;.;.
Eigen
Pathogenic
0.84
Eigen_PC
Pathogenic
0.81
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.96
D;D;D;D
M_CAP
Benign
0.022
T
MetaRNN
Benign
0.15
T;T;T;T
MetaSVM
Benign
-1.2
T
MutationAssessor
Uncertain
2.6
M;.;.;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
-2.1
N;N;N;N
REVEL
Uncertain
0.35
Sift
Benign
0.050
D;D;T;D
Sift4G
Benign
0.16
T;T;T;T
Polyphen
1.0
D;.;.;.
Vest4
0.88
MVP
0.50
MPC
0.64
ClinPred
0.15
T
GERP RS
5.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.20
gMVP
0.56

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: rs200764787; hg19: chr1-201966652; COSMIC: COSV55241650; COSMIC: COSV55241650; API