Variant chr1-98956645-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.334A>G(p.Ile112Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000483 in 1,449,592 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

PLPPR5
NM_001037317.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.986

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=0.18635541).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PLPPR5	NM_001037317.2 linkuse as main transcript	c.334A>G	p.Ile112Val	missense_variant	2/6	ENST00000263177.5
PLPPR5	NM_001010861.3 linkuse as main transcript	c.334A>G	p.Ile112Val	missense_variant	2/6
PLPPR5	XM_011540838.4 linkuse as main transcript	c.286A>G	p.Ile96Val	missense_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLPPR5	ENST00000263177.5 linkuse as main transcript	c.334A>G	p.Ile112Val	missense_variant	2/6	1	NM_001037317.2	P4	Q32ZL2-1
PLPPR5	ENST00000370188.7 linkuse as main transcript	c.334A>G	p.Ile112Val	missense_variant	2/6	1		A1	Q32ZL2-2
PLPPR5	ENST00000672681.1 linkuse as main transcript	c.334A>G	p.Ile112Val	missense_variant	2/7
PLPPR5	ENST00000696571.1 linkuse as main transcript	c.169A>G	p.Ile57Val	missense_variant	3/7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000483

AC:

AN:

1449592

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

720824

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000542

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

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 12, 2023

The c.334A>G (p.I112V) alteration is located in exon 2 (coding exon 2) of the PLPPR5 gene. This alteration results from a A to G substitution at nucleotide position 334, causing the isoleucine (I) at amino acid position 112 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

0.14

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.014

.;T

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.062

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.85

D;D

M_CAP

Benign

0.0056

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.50

N;N

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.56

N;N

REVEL

Benign

0.055

Sift

Benign

0.47

T;T

Sift4G

Benign

0.50

T;T

Polyphen

0.0030

B;B

Vest4

0.26

MutPred

0.61

Loss of catalytic residue at P114 (P = 0.08);Loss of catalytic residue at P114 (P = 0.08);

MVP

0.043

MPC

0.49

ClinPred

0.39

GERP RS

4.7

Varity_R

0.12

gMVP

0.54

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over