Genetic Variant PPEF2:p.Arg548Lys (chr4-75872031-C-T) – 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_006239.3(PPEF2):c.1643G>A(p.Arg548Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000278 in 1,440,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

PPEF2
NM_006239.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.45

Publications

0 publications found

Variant links:

Genes affected

PPEF2 (HGNC:9244): (protein phosphatase with EF-hand domain 2) This gene encodes a member of the serine/threonine protein phosphatase with EF-hand motif family. The protein contains a protein phosphatase catalytic domain, and at least two EF-hand calcium-binding motifs in its C terminus. Although its substrate(s) is unknown, the encoded protein, which is expressed specifically in photoreceptors and the pineal, has been suggested to play a role in the visual system. This gene shares high sequence similarity with the Drosophila retinal degeneration C (rdgC) gene. [provided by RefSeq, Jul 2008]

PPEF2 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=0.16099429).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006239.3. 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
	PPEF2	NM_006239.3	MANE Select	c.1643G>A	p.Arg548Lys	missense	Exon 13 of 17	NP_006230.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PPEF2	ENST00000286719.12	TSL:1 MANE Select	c.1643G>A	p.Arg548Lys	missense	Exon 13 of 17	ENSP00000286719.6	O14830-1
PPEF2	ENST00000511880.7	TSL:1	n.*1881G>A		non_coding_transcript_exon	Exon 14 of 18	ENSP00000426186.2	E7EPQ9
PPEF2	ENST00000511880.7	TSL:1	n.*1881G>A		3_prime_UTR	Exon 14 of 18	ENSP00000426186.2	E7EPQ9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000432

AC:

AN:

231560

AF XY:

0.00000799

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:

0.00

Gnomad OTH exome

AF:

0.000179

GnomAD4 exome

AF:

0.00000278

AC:

AN:

1440134

Hom.:

Cov.:

AF XY:

0.00000279

AC XY:

AN XY:

715768

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32298

American (AMR)

AF:

0.0000262

AC:

AN:

38230

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25010

East Asian (EAS)

AF:

0.00

AC:

AN:

39404

South Asian (SAS)

AF:

0.00

AC:

AN:

81446

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53164

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5674

European-Non Finnish (NFE)

AF:

0.00000271

AC:

AN:

1105424

Other (OTH)

AF:

0.00

AC:

AN:

59484

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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.:

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

0.093

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.083

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.20

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.67

M_CAP

Benign

0.0069

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.4

PhyloP100

1.4

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.3

REVEL

Benign

0.090

Sift

Benign

0.27

Sift4G

Benign

0.25

Polyphen

0.28

Vest4

0.31

MutPred

0.45

Gain of ubiquitination at R548 (P = 0.0267)

MVP

0.45

MPC

0.23

ClinPred

0.20

GERP RS

2.9

Varity_R

0.11

gMVP

0.64

Mutation Taster

=95/5

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