Variant 1-98956630-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001037317.2(PLPPR5):c.349C>T(p.Arg117Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000221 in 1,586,096 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

PLPPR5
NM_001037317.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.85

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PLPPR5	NM_001037317.2 linkuse as main transcript	c.349C>T	p.Arg117Cys	missense_variant	2/6	ENST00000263177.5	NP_001032394.1
PLPPR5	NM_001010861.3 linkuse as main transcript	c.349C>T	p.Arg117Cys	missense_variant	2/6		NP_001010861.1
PLPPR5	XM_011540838.4 linkuse as main transcript	c.301C>T	p.Arg101Cys	missense_variant	3/7		XP_011539140.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLPPR5	ENST00000263177.5 linkuse as main transcript	c.349C>T	p.Arg117Cys	missense_variant	2/6	1	NM_001037317.2	ENSP00000263177	P4	Q32ZL2-1
PLPPR5	ENST00000370188.7 linkuse as main transcript	c.349C>T	p.Arg117Cys	missense_variant	2/6	1		ENSP00000359207	A1	Q32ZL2-2
PLPPR5	ENST00000672681.1 linkuse as main transcript	c.349C>T	p.Arg117Cys	missense_variant	2/7			ENSP00000500930
PLPPR5	ENST00000696571.1 linkuse as main transcript	c.184C>T	p.Arg62Cys	missense_variant	3/7			ENSP00000512726

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152100

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000177

AC:

AN:

225916

Hom.:

AF XY:

0.000163

AC XY:

AN XY:

122946

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000372

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000379

Gnomad FIN exome

AF:

0.000567

Gnomad NFE exome

AF:

0.000236

Gnomad OTH exome

AF:

0.000186

GnomAD4 exome

AF:

0.000233

AC:

334

AN:

1433878

Hom.:

Cov.:

AF XY:

0.000232

AC XY:

165

AN XY:

712700

show subpopulations

Gnomad4 AFR exome

AF:

0.0000631

Gnomad4 AMR exome

AF:

0.0000527

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000250

Gnomad4 FIN exome

AF:

0.000472

Gnomad4 NFE exome

AF:

0.000267

Gnomad4 OTH exome

AF:

0.000152

GnomAD4 genome

AF:

0.000112

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000248

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.000132

AC:

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

Oct 20, 2023

The c.349C>T (p.R117C) alteration is located in exon 2 (coding exon 2) of the PLPPR5 gene. This alteration results from a C to T substitution at nucleotide position 349, causing the arginine (R) at amino acid position 117 to be replaced by a cysteine (C). 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

Pathogenic

0.84

BayesDel_addAF

Uncertain

0.048

BayesDel_noAF

Pathogenic

0.15

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.24

.;T

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.94

LIST_S2

Pathogenic

0.99

D;D

M_CAP

Benign

0.084

MetaRNN

Uncertain

0.70

D;D

MetaSVM

Benign

-0.50

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.85

PROVEAN

Pathogenic

-6.9

D;D

REVEL

Uncertain

0.47

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;D

Vest4

0.89

MVP

0.42

MPC

1.8

ClinPred

0.70

GERP RS

3.8

Varity_R

0.74

gMVP

0.92

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