Variant chr1-201982686-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_020216.4(RNPEP):c.20C>T(p.Ser7Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000648 in 1,389,732 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

RNPEP
NM_020216.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.728

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]

RNPEP links:

RNPEP (HGNC:):

RNPEP links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity AMPB_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07714376).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNPEP	NM_020216.4 linkuse as main transcript	c.20C>T	p.Ser7Phe	missense_variant	1/11	ENST00000295640.9	NP_064601.3	Q9H4A4
RNPEP	NM_001319183.2 linkuse as main transcript	c.-848C>T		5_prime_UTR_variant	1/10		NP_001306112.1	Q9H4A4
RNPEP	NM_001319184.2 linkuse as main transcript	c.-702C>T		5_prime_UTR_variant	1/10		NP_001306113.1	Q9H4A4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RNPEP	ENST00000295640.9 linkuse as main transcript	c.20C>T	p.Ser7Phe	missense_variant	1/11	1	NM_020216.4	ENSP00000295640.4	Q9H4A4
RNPEP	ENST00000367286.7 linkuse as main transcript	c.20C>T	p.Ser7Phe	missense_variant	1/10	5		ENSP00000356255.3	A6NKB8
RNPEP	ENST00000481780.5 linkuse as main transcript	n.66+249C>T		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151394

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000485

AC:

AN:

1238338

Hom.:

Cov.:

AF XY:

0.00000329

AC XY:

AN XY:

607520

show subpopulations

Gnomad4 AFR exome

AF:

0.0000408

Gnomad4 AMR exome

AF:

0.000118

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:

0.00000200

Gnomad4 OTH exome

AF:

0.0000202

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151394

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73932

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

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

Aug 12, 2024

The c.20C>T (p.S7F) alteration is located in exon 1 (coding exon 1) of the RNPEP gene. This alteration results from a C to T substitution at nucleotide position 20, causing the serine (S) at amino acid position 7 to be replaced by a phenylalanine (F). 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

0.094

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.11

T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.089

LIST_S2

Benign

0.53

T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.077

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.81

L;.

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.55

N;N

REVEL

Benign

0.041

Sift

Uncertain

0.020

D;D

Sift4G

Uncertain

0.047

D;D

Polyphen

0.12

B;.

Vest4

0.20

MutPred

0.23

Loss of glycosylation at S7 (P = 0.0061);Loss of glycosylation at S7 (P = 0.0061);

MVP

0.22

MPC

0.17

ClinPred

0.059

GERP RS

-0.011

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.073

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.

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