Variant 2-240568651-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_018226.6(RNPEPL1):c.65C>T(p.Pro22Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000526 in 1,010,632 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00058 ( 0 hom. )

Consequence

RNPEPL1
NM_018226.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.187

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]

RNPEPL1 links:

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]

ANKMY1 links:

ANKMY1 (HGNC:):

ANKMY1 links:

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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	Protein	UniProt
RNPEPL1	NM_018226.6 linkuse as main transcript	c.65C>T	p.Pro22Leu	missense_variant	1/11	ENST00000270357.10	NP_060696.4	Q9HAU8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RNPEPL1	ENST00000270357.10 linkuse as main transcript	c.65C>T	p.Pro22Leu	missense_variant	1/11	1	NM_018226.6	ENSP00000270357.4	Q9HAU8
ANKMY1	ENST00000418708.3 linkuse as main transcript	c.-122+385G>A		intron_variant		3		ENSP00000407015.1	C9JZ56
RNPEPL1	ENST00000451363.5 linkuse as main transcript	c.-57+2710C>T		intron_variant		4		ENSP00000414661.1	C9JSI2
ANKMY1	ENST00000418505.3 linkuse as main transcript	n.174+385G>A		intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.000186

AC:

AN:

145406

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000495

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000418

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00336

Gnomad NFE

AF:

0.000336

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000585

AC:

506

AN:

865114

Hom.:

Cov.:

AF XY:

0.000590

AC XY:

239

AN XY:

405172

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000526

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000682

Gnomad4 FIN exome

AF:

0.000387

Gnomad4 NFE exome

AF:

0.000608

Gnomad4 OTH exome

AF:

0.000485

GnomAD4 genome

AF:

0.000179

AC:

AN:

145518

Hom.:

Cov.:

AF XY:

0.000127

AC XY:

AN XY:

70796

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:

0.000418

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000320

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000108

Hom.:

Bravo

AF:

0.000174

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

Sep 16, 2021

The c.65C>T (p.P22L) 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 65, causing the proline (P) at amino acid position 22 to be replaced by a leucine (L). 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_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.10

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.49

MetaRNN

Uncertain

0.47

PrimateAI

Pathogenic

0.81

PROVEAN

Pathogenic

-8.4

Sift

Uncertain

0.0010

GERP RS

0.98

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

3.5

Varity_R

0.10

gMVP

0.39

Splicing

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