chr2-240568791-C-T

Variant summary

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

The NM_018226.6(RNPEPL1):​c.205C>T​(p.Arg69Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000121 in 1,075,490 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000021 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

RNPEPL1
NM_018226.6 missense

Scores

1
1
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.122
Variant links:
Genes affected
RNPEPL1 (HGNC:10079): (arginyl aminopeptidase like 1) Enables metalloaminopeptidase activity. Involved in proteolysis. [provided by Alliance of Genome Resources, Apr 2022]
ANKMY1 (HGNC:20987): (ankyrin repeat and MYND domain containing 1) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

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=0.2834388).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RNPEPL1NM_018226.6 linkc.205C>T p.Arg69Trp missense_variant Exon 1 of 11 ENST00000270357.10 NP_060696.4 Q9HAU8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RNPEPL1ENST00000270357.10 linkc.205C>T p.Arg69Trp missense_variant Exon 1 of 11 1 NM_018226.6 ENSP00000270357.4 Q9HAU8

Frequencies

GnomAD3 genomes
AF:
0.0000206
AC:
3
AN:
145920
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000494
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:
0.0000152
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000108
AC:
10
AN:
929570
Hom.:
0
Cov.:
31
AF XY:
0.00000908
AC XY:
4
AN XY:
440440
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:
0.000109
Gnomad4 NFE exome
AF:
0.0000110
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000206
AC:
3
AN:
145920
Hom.:
0
Cov.:
32
AF XY:
0.0000141
AC XY:
1
AN XY:
70946
show subpopulations
Gnomad4 AFR
AF:
0.0000494
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:
0.0000152
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
Mar 19, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.205C>T (p.R69W) alteration is located in exon 1 (coding exon 1) of the RNPEPL1 gene. This alteration results from a C to T substitution at nucleotide position 205, causing the arginine (R) at amino acid position 69 to be replaced by a tryptophan (W). 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
0.30
BayesDel_noAF
Benign
-0.33
CADD
Uncertain
24
DANN
Uncertain
0.98
FATHMM_MKL
Benign
0.42
N
LIST_S2
Benign
0.66
T
MetaRNN
Benign
0.28
T
PrimateAI
Pathogenic
0.88
D
GERP RS
1.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.31
gMVP
0.36

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: rs1480773280; hg19: chr2-241508208; API