Genetic Variant RFPL1:p.Leu138Val (chr22-29441580-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_021026.2(RFPL1):c.412C>G(p.Leu138Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L138F) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

RFPL1
NM_021026.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.61

Publications

1 publications found

Variant links:

Genes affected

RFPL1 (HGNC:9977): (ret finger protein like 1) Predicted to enable ubiquitin-protein transferase activity. Involved in several processes, including negative regulation of G2/M transition of mitotic cell cycle; negative regulation of cell division; and positive regulation of proteolysis. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RFPL1 links:

RFPL1S (HGNC:9978): (RFPL1 antisense RNA 1)

RFPL1S links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.76

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021026.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RFPL1	NM_021026.2	MANE Select	c.412C>G	p.Leu138Val	missense	Exon 2 of 2	NP_066306.2	O75677
RFPL1	NM_001393612.1		c.325C>G	p.Leu109Val	missense	Exon 10 of 10	NP_001380541.1
RFPL1S	NR_002727.2		n.550G>C		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RFPL1	ENST00000354373.2	TSL:1 MANE Select	c.412C>G	p.Leu138Val	missense	Exon 2 of 2	ENSP00000346342.2	O75677
RFPL1S	ENST00000248980.9	TSL:1	n.272-2387G>C		intron	N/A
RFPL1S	ENST00000461286.4	TSL:4	n.857G>C		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.000174

AC:

AN:

68978

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000393

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000213

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

GnomAD2 exomes

AF:

0.0000439

AC:

AN:

250490

AF XY:

0.0000296

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.0000581

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:

0.0000339

AC:

AN:

530582

Hom.:

Cov.:

AF XY:

0.0000266

AC XY:

AN XY:

263560

show subpopulations

African (AFR)

AF:

0.000632

AC:

AN:

23734

American (AMR)

AF:

0.0000587

AC:

AN:

17030

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5570

East Asian (EAS)

AF:

0.00

AC:

AN:

31232

South Asian (SAS)

AF:

0.00

AC:

AN:

38244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26040

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1678

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

364768

Other (OTH)

AF:

0.0000897

AC:

AN:

22286

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

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:

0.000174

AC:

AN:

68978

Hom.:

Cov.:

AF XY:

0.000176

AC XY:

AN XY:

34068

show subpopulations

African (AFR)

AF:

0.000393

AC:

AN:

28008

American (AMR)

AF:

0.000213

AC:

AN:

4690

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

716

East Asian (EAS)

AF:

0.00

AC:

AN:

4118

South Asian (SAS)

AF:

0.00

AC:

AN:

2324

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

22504

Other (OTH)

AF:

0.00

AC:

AN:

766

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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.:

ExAC

AF:

0.0000308

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

Eigen

Benign

-0.083

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.19

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.0038

MetaRNN

Pathogenic

0.76

MetaSVM

Benign

-0.85

MutationAssessor

Pathogenic

3.2

PhyloP100

2.6

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.12

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.011

Polyphen

1.0

Vest4

0.30

MutPred

0.83

Loss of sheet (P = 0.0817)

MVP

0.50

MPC

0.67

ClinPred

0.40

GERP RS

-0.012

Varity_R

0.74

gMVP

0.11

Mutation Taster

=100/0

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