Variant chrX-18779018-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001377996.1(PPEF1):c.567C>T(p.Leu189Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00402 in 1,194,298 control chromosomes in the GnomAD database, including 122 homozygotes. There are 1,262 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 58 hom., 590 hem., cov: 23)

Exomes 𝑓: 0.0024 ( 64 hom. 672 hem. )

Consequence

PPEF1
NM_001377996.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.499

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant X-18779018-C-T is Benign according to our data. Variant chrX-18779018-C-T is described in ClinVar as [Benign]. Clinvar id is 714921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.499 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPEF1	NM_001377996.1 linkuse as main transcript	c.567C>T	p.Leu189Leu	synonymous_variant	7/16	ENST00000470157.2	NP_001364925.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPEF1	ENST00000470157.2 linkuse as main transcript	c.567C>T	p.Leu189Leu	synonymous_variant	7/16	3	NM_001377996.1	ENSP00000419273.2		O14829-1H7C592

Frequencies

GnomAD3 genomes

AF:

0.0201

AC:

2240

AN:

111169

Hom.:

Cov.:

AF XY:

0.0174

AC XY:

582

AN XY:

33375

show subpopulations

Gnomad AFR

AF:

0.0691

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00776

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000771

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00422

Gnomad NFE

AF:

0.000396

Gnomad OTH

AF:

0.0193

GnomAD3 exomes

AF:

0.00619

AC:

1109

AN:

179135

Hom.:

AF XY:

0.00446

AC XY:

285

AN XY:

63843

show subpopulations

Gnomad AFR exome

AF:

0.0742

Gnomad AMR exome

AF:

0.00368

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000226

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000298

Gnomad OTH exome

AF:

0.00317

GnomAD4 exome

AF:

0.00236

AC:

2554

AN:

1083077

Hom.:

Cov.:

AF XY:

0.00191

AC XY:

672

AN XY:

352637

show subpopulations

Gnomad4 AFR exome

AF:

0.0749

Gnomad4 AMR exome

AF:

0.00441

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000283

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000180

Gnomad4 OTH exome

AF:

0.00599

GnomAD4 genome

AF:

0.0202

AC:

2249

AN:

111221

Hom.:

Cov.:

AF XY:

0.0176

AC XY:

590

AN XY:

33437

show subpopulations

Gnomad4 AFR

AF:

0.0692

Gnomad4 AMR

AF:

0.00775

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000774

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000396

Gnomad4 OTH

AF:

0.0191

Alfa

AF:

0.0118

Hom.:

Bravo

AF:

0.0238

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 18, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

4.3

DANN

Benign

0.65

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over