dbSNP rs369525525: PLPPR5:p.Val79Leu (chr1-99004437-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001037317.2(PLPPR5):c.235G>T(p.Val79Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000187 in 1,602,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PLPPR5
NM_001037317.2 missense, splice_region

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.16

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:

PLPPR5-AS1 (HGNC:55720): (PLPPR5 antisense RNA 1)

PLPPR5-AS1 links:

Genome browser will be placed here

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=0.11336386).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLPPR5	NM_001037317.2 link	c.235G>T	p.Val79Leu	missense_variant, splice_region_variant	Exon 1 of 6	ENST00000263177.5	NP_001032394.1	Q32ZL2-1
PLPPR5	NM_001010861.3 link	c.235G>T	p.Val79Leu	missense_variant, splice_region_variant	Exon 1 of 6		NP_001010861.1	Q32ZL2-2
PLPPR5	XM_011540838.4 link	c.187G>T	p.Val63Leu	missense_variant, splice_region_variant	Exon 2 of 7		XP_011539140.1
PLPPR5-AS1	NR_033940.1 link	n.162C>A		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLPPR5	ENST00000263177.5 link	c.235G>T	p.Val79Leu	missense_variant, splice_region_variant	Exon 1 of 6	1	NM_001037317.2	ENSP00000263177.4		Q32ZL2-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152212

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000434

AC:

AN:

230284

Hom.:

AF XY:

0.00000792

AC XY:

AN XY:

126314

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 SAS exome

AF:

0.0000341

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1450508

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

720768

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74358

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:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.019

.;T

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.087

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.64

T;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.58

N;N

REVEL

Benign

0.042

Sift

Benign

0.28

T;T

Sift4G

Benign

0.40

T;T

Polyphen

0.0080

B;B

Vest4

0.19

MutPred

0.48

Loss of stability (P = 0.1602);Loss of stability (P = 0.1602);

MVP

0.043

MPC

0.57

ClinPred

0.23

GERP RS

4.3

Varity_R

0.12

gMVP

0.70

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over