Genetic Variant NM_018226.6:c.320C>T (chr2-240568906-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_018226.6(RNPEPL1):c.320C>T(p.Ser107Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000344 in 1,278,450 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S107C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

RNPEPL1
NM_018226.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.701

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.25874633).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018226.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNPEPL1	NM_018226.6	MANE Select	c.320C>T	p.Ser107Phe	missense	Exon 1 of 11	NP_060696.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RNPEPL1	ENST00000270357.10	TSL:1 MANE Select	c.320C>T	p.Ser107Phe	missense	Exon 1 of 11	ENSP00000270357.4	Q9HAU8
RNPEPL1	ENST00000971323.1		c.320C>T	p.Ser107Phe	missense	Exon 1 of 11	ENSP00000641382.1
RNPEPL1	ENST00000971322.1		c.320C>T	p.Ser107Phe	missense	Exon 1 of 11	ENSP00000641381.1

Frequencies

GnomAD3 genomes

AF:

0.0000602

AC:

AN:

149598

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000734

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000266

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:

0.0000297

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000319

AC:

AN:

1128740

Hom.:

Cov.:

AF XY:

0.0000365

AC XY:

AN XY:

547352

show subpopulations

African (AFR)

AF:

0.0000886

AC:

AN:

22578

American (AMR)

AF:

0.00148

AC:

AN:

8790

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14264

East Asian (EAS)

AF:

0.00

AC:

AN:

25146

South Asian (SAS)

AF:

0.0000278

AC:

AN:

35916

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23846

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2976

European-Non Finnish (NFE)

AF:

0.0000200

AC:

AN:

950518

Other (OTH)

AF:

0.0000224

AC:

AN:

44706

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.536

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

AF:

0.0000534

AC:

AN:

149710

Hom.:

Cov.:

AF XY:

0.0000410

AC XY:

AN XY:

73108

show subpopulations

African (AFR)

AF:

0.0000488

AC:

AN:

41012

American (AMR)

AF:

0.000265

AC:

AN:

15066

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3454

East Asian (EAS)

AF:

0.00

AC:

AN:

5066

South Asian (SAS)

AF:

0.00

AC:

AN:

4772

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9860

Middle Eastern (MID)

AF:

0.00

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.0000297

AC:

AN:

67228

Other (OTH)

AF:

0.00

AC:

AN:

2078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

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

0.21

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

0.97

DEOGEN2

Benign

0.13

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.36

MetaRNN

Benign

0.26

PhyloP100

-0.70

PrimateAI

Pathogenic

0.87

PROVEAN

Uncertain

-3.2

Sift

Uncertain

0.0010

GERP RS

2.2

PromoterAI

-0.089

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Varity_R

0.097

gMVP

0.42

Mutation Taster

=296/4

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over