Genetic Variant RPF2:p.Cys87Ser (chr6-110997208-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_032194.3(RPF2):c.260G>C(p.Cys87Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000277 in 1,446,284 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: 0.0000028 ( 0 hom. )

Consequence

RPF2
NM_032194.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.51

Publications

0 publications found

Variant links:

Genes affected

RPF2 (HGNC:20870): (ribosome production factor 2 homolog) Enables 5S rRNA binding activity. Involved in protein localization to nucleolus; regulation of signal transduction by p53 class mediator; and ribosomal large subunit biogenesis. Located in chromosome; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RPF2 links:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37371433).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032194.3. 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
	RPF2	NM_032194.3	MANE Select	c.260G>C	p.Cys87Ser	missense	Exon 5 of 10	NP_115570.1	Q9H7B2
	RPF2	NM_001289111.2		c.71G>C	p.Cys24Ser	missense	Exon 4 of 9	NP_001276040.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPF2	ENST00000441448.7	TSL:1 MANE Select	c.260G>C	p.Cys87Ser	missense	Exon 5 of 10	ENSP00000402338.2	Q9H7B2
RPF2	ENST00000607388.1	TSL:1	n.*42G>C		non_coding_transcript_exon	Exon 4 of 9	ENSP00000476081.1	U3KQN5
RPF2	ENST00000607388.1	TSL:1	n.*42G>C		3_prime_UTR	Exon 4 of 9	ENSP00000476081.1	U3KQN5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000405

AC:

AN:

247090

AF XY:

0.00

show subpopulations

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:

0.00000898

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000277

AC:

AN:

1446284

Hom.:

Cov.:

AF XY:

0.00000417

AC XY:

AN XY:

720164

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33174

American (AMR)

AF:

0.00

AC:

AN:

44480

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25844

East Asian (EAS)

AF:

0.00

AC:

AN:

39608

South Asian (SAS)

AF:

0.00

AC:

AN:

85618

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53196

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5204

European-Non Finnish (NFE)

AF:

0.00000364

AC:

AN:

1099414

Other (OTH)

AF:

0.00

AC:

AN:

59746

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

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:

0.0000251

Hom.:

Bravo

AF:

0.0000189

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

Uncertain

0.45

BayesDel_addAF

Uncertain

0.090

BayesDel_noAF

Benign

-0.11

CADD

Benign

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.027

Eigen

Benign

0.00044

Eigen_PC

Benign

0.19

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.013

MetaRNN

Benign

0.37

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PhyloP100

7.5

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.2

REVEL

Benign

0.16

Sift

Benign

0.44

Sift4G

Benign

0.61

Polyphen

0.0090

Vest4

0.76

MutPred

0.60

Gain of disorder (P = 2e-04)

MVP

0.40

MPC

0.21

ClinPred

0.40

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.25

gMVP

0.78

Mutation Taster

=64/36

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