Variant chr1-98921896-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001037317.2(PLPPR5):c.784A>G(p.Ile262Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000198 in 1,612,868 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: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

PLPPR5
NM_001037317.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.80

Variant links:

Genes affected

PLPPR5 (HGNC:31703): (phospholipid phosphatase related 5) The protein encoded by this gene is a type 2 member of the phosphatidic acid phosphatase (PAP) family. All type 2 members of this protein family contain 6 transmembrane regions, and a consensus N-glycosylation site. PAPs convert phosphatidic acid to diacylglycerol, and function in de novo synthesis of glycerolipids as well as in receptor-activated signal transduction mediated by phospholipase D. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

PLPPR5 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24925372).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PLPPR5	NM_001037317.2 linkuse as main transcript	c.784A>G	p.Ile262Val	missense_variant	4/6	ENST00000263177.5	NP_001032394.1
PLPPR5	NM_001010861.3 linkuse as main transcript	c.784A>G	p.Ile262Val	missense_variant	4/6		NP_001010861.1
PLPPR5	XM_011540838.4 linkuse as main transcript	c.736A>G	p.Ile246Val	missense_variant	5/7		XP_011539140.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLPPR5	ENST00000263177.5 linkuse as main transcript	c.784A>G	p.Ile262Val	missense_variant	4/6	1	NM_001037317.2	ENSP00000263177	P4	Q32ZL2-1
PLPPR5	ENST00000370188.7 linkuse as main transcript	c.784A>G	p.Ile262Val	missense_variant	4/6	1		ENSP00000359207	A1	Q32ZL2-2
PLPPR5	ENST00000672681.1 linkuse as main transcript	c.784A>G	p.Ile262Val	missense_variant	4/7			ENSP00000500930
PLPPR5	ENST00000696571.1 linkuse as main transcript	c.619A>G	p.Ile207Val	missense_variant	5/7			ENSP00000512726

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250160

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135244

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000185

AC:

AN:

1460654

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

726650

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000225

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000565

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 30, 2023

The c.784A>G (p.I262V) alteration is located in exon 4 (coding exon 4) of the PLPPR5 gene. This alteration results from a A to G substitution at nucleotide position 784, causing the isoleucine (I) at amino acid position 262 to be replaced by a valine (V). 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

0.094

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

.;T

Eigen

Benign

0.098

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.024

MetaRNN

Benign

0.25

T;T

MetaSVM

Benign

-0.79

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.46

N;N

REVEL

Uncertain

0.30

Sift

Benign

0.38

T;T

Sift4G

Benign

0.56

T;T

Polyphen

0.47

P;P

Vest4

0.27

MutPred

0.53

Loss of helix (P = 0.028);Loss of helix (P = 0.028);

MVP

0.068

MPC

0.29

ClinPred

0.58

GERP RS

5.5

Varity_R

0.12

gMVP

0.46

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