Genetic Variant RNPEP:p.Gly145Glu (chr1-201983100-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020216.4(RNPEP):c.434G>A(p.Gly145Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000816 in 1,348,064 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: not found (cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

RNPEP
NM_020216.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.75

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2575035).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020216.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
RNPEP	NM_020216.4	MANE Select	c.434G>A	p.Gly145Glu	missense	Exon 1 of 11	NP_064601.3
RNPEP	NM_001319183.2		c.-434G>A		5_prime_UTR	Exon 1 of 10	NP_001306112.1
RNPEP	NM_001319184.2		c.-288G>A		5_prime_UTR	Exon 1 of 10	NP_001306113.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RNPEP	ENST00000295640.9	TSL:1 MANE Select	c.434G>A	p.Gly145Glu	missense	Exon 1 of 11	ENSP00000295640.4	Q9H4A4
RNPEP	ENST00000471105.5	TSL:1	n.146G>A		non_coding_transcript_exon	Exon 1 of 10
RNPEP	ENST00000967255.1		c.434G>A	p.Gly145Glu	missense	Exon 1 of 11	ENSP00000637314.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

99304

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000816

AC:

AN:

1348064

Hom.:

Cov.:

AF XY:

0.00000451

AC XY:

AN XY:

665196

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28614

American (AMR)

AF:

0.00

AC:

AN:

29002

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21730

East Asian (EAS)

AF:

0.00

AC:

AN:

33510

South Asian (SAS)

AF:

0.00

AC:

AN:

72274

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37002

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4268

European-Non Finnish (NFE)

AF:

0.00000938

AC:

AN:

1065832

Other (OTH)

AF:

0.0000179

AC:

AN:

55832

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000340

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.087

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.80

M_CAP

Benign

0.038

MetaRNN

Benign

0.26

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.1

PhyloP100

2.8

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.1

REVEL

Benign

0.10

Sift

Benign

0.13

Sift4G

Benign

0.45

Polyphen

0.86

Vest4

0.32

MutPred

0.53

Loss of sheet (P = 0.0817)

MVP

0.43

MPC

0.49

ClinPred

0.81

GERP RS

4.0

PromoterAI

0.0070

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.12

gMVP

0.60

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over