dbSNP rs2046028908: PPEF1:p.Pro195Leu (chrX-18779035-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001377996.1(PPEF1):c.584C>T(p.Pro195Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000025 in 1,199,592 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.0000018 ( 0 hom. 2 hem. )

Consequence

PPEF1
NM_001377996.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.10

Publications

0 publications found

Variant links:

Genes affected

PPEF1 (HGNC:9243): (protein phosphatase with EF-hand domain 1) 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 has been suggested to play a role in specific sensory neuron function and/or development. This gene shares high sequence similarity with the Drosophila retinal degeneration C (rdgC) gene. Several alternatively spliced transcript variants, each encoding a distinct isoform, have been described. [provided by RefSeq, Jul 2008]

PPEF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPEF1	NM_001377996.1 link	c.584C>T	p.Pro195Leu	missense_variant	Exon 7 of 16	ENST00000470157.2	NP_001364925.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPEF1	ENST00000470157.2 link	c.584C>T	p.Pro195Leu	missense_variant	Exon 7 of 16	3	NM_001377996.1	ENSP00000419273.2		O14829-1H7C592

Frequencies

GnomAD3 genomes

AF:

0.00000900

AC:

AN:

111168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000327

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

GnomAD4 exome

AF:

0.00000184

AC:

AN:

1088424

Hom.:

Cov.:

AF XY:

0.00000561

AC XY:

AN XY:

356290

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26175

American (AMR)

AF:

0.00

AC:

AN:

35144

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19293

East Asian (EAS)

AF:

0.00

AC:

AN:

30163

South Asian (SAS)

AF:

0.0000187

AC:

AN:

53615

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40492

Middle Eastern (MID)

AF:

0.000243

AC:

AN:

4116

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

833640

Other (OTH)

AF:

0.00

AC:

AN:

45786

GnomAD4 genome

AF:

0.00000900

AC:

AN:

111168

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33364

show subpopulations

African (AFR)

AF:

0.0000327

AC:

AN:

30550

American (AMR)

AF:

0.00

AC:

AN:

10426

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2639

East Asian (EAS)

AF:

0.00

AC:

AN:

3558

South Asian (SAS)

AF:

0.00

AC:

AN:

2587

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5941

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53045

Other (OTH)

AF:

0.00

AC:

AN:

1505

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 15, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.584C>T (p.P195L) alteration is located in exon 10 (coding exon 7) of the PPEF1 gene. This alteration results from a C to T substitution at nucleotide position 584, causing the proline (P) at amino acid position 195 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

0.0052

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.78

D;.;.

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.74

T;T;D

M_CAP

Uncertain

0.10

MetaRNN

Uncertain

0.46

T;T;T

MetaSVM

Uncertain

0.15

MutationAssessor

Uncertain

2.3

M;M;.

PhyloP100

1.1

PrimateAI

Benign

0.30

PROVEAN

Pathogenic

-6.7

D;D;D

REVEL

Uncertain

0.35

Sift

Uncertain

0.0030

D;D;D

Sift4G

Uncertain

0.019

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.22

MutPred

0.45

Loss of disorder (P = 0.0377);Loss of disorder (P = 0.0377);.;

MVP

0.54

MPC

0.90

ClinPred

0.96

GERP RS

3.1

Varity_R

0.26

gMVP

0.85

Mutation Taster

=85/15

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over