1-98922056-C-T

Position:

chr1-98922056-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001037317.2(PLPPR5):c.624G>A(p.Met208Ile) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000189 in 1,586,480 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PLPPR5
NM_001037317.2 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.57

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.835

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PLPPR5	NM_001037317.2 linkuse as main transcript	c.624G>A	p.Met208Ile	missense_variant, splice_region_variant	4/6	ENST00000263177.5
PLPPR5	NM_001010861.3 linkuse as main transcript	c.624G>A	p.Met208Ile	missense_variant, splice_region_variant	4/6
PLPPR5	XM_011540838.4 linkuse as main transcript	c.576G>A	p.Met192Ile	missense_variant, splice_region_variant	5/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLPPR5	ENST00000263177.5 linkuse as main transcript	c.624G>A	p.Met208Ile	missense_variant, splice_region_variant	4/6	1	NM_001037317.2	P4	Q32ZL2-1
PLPPR5	ENST00000370188.7 linkuse as main transcript	c.624G>A	p.Met208Ile	missense_variant, splice_region_variant	4/6	1		A1	Q32ZL2-2
PLPPR5	ENST00000672681.1 linkuse as main transcript	c.624G>A	p.Met208Ile	missense_variant, splice_region_variant	4/7
PLPPR5	ENST00000696571.1 linkuse as main transcript	c.459G>A	p.Met153Ile	missense_variant, splice_region_variant	5/7

Frequencies

GnomAD3 genomes

AF:

0.00000786

AC:

AN:

127212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000170

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000461

AC:

AN:

216740

Hom.:

AF XY:

0.00000850

AC XY:

AN XY:

117704

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000981

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459268

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725838

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000786

AC:

AN:

127212

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

61072

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000170

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000370

Hom.:

ExAC

AF:

0.00000824

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

Aug 17, 2022

The c.624G>A (p.M208I) alteration is located in exon 4 (coding exon 4) of the PLPPR5 gene. This alteration results from a G to A substitution at nucleotide position 624, causing the methionine (M) at amino acid position 208 to be replaced by an isoleucine (I). 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

0.90

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.10

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.63

.;D

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.85

D;D

M_CAP

Benign

0.046

MetaRNN

Pathogenic

0.83

D;D

MetaSVM

Benign

-0.90

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-3.1

D;D

REVEL

Uncertain

0.41

Sift

Uncertain

0.0060

D;D

Sift4G

Benign

0.13

T;T

Polyphen

0.94

P;P

Vest4

0.83

MutPred

0.64

Gain of catalytic residue at M208 (P = 0.028);Gain of catalytic residue at M208 (P = 0.028);

MVP

0.54

MPC

0.51

ClinPred

0.98

GERP RS

5.4

Varity_R

0.51

gMVP

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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