Variant 16-68245541-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_012320.4(PLA2G15):c.115C>G(p.Pro39Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000253 in 1,583,804 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

PLA2G15
NM_012320.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.09

Variant links:

Genes affected

PLA2G15 (HGNC:17163): (phospholipase A2 group XV) Lysophospholipases are enzymes that act on biological membranes to regulate the multifunctional lysophospholipids. The protein encoded by this gene hydrolyzes lysophosphatidylcholine to glycerophosphorylcholine and a free fatty acid. This enzyme is present in the plasma and thought to be associated with high-density lipoprotein. A later paper contradicts the function of this gene. It demonstrates that this gene encodes a lysosomal enzyme instead of a lysophospholipase and has both calcium-independent phospholipase A2 and transacylase activities. [provided by RefSeq, Jul 2008]

PLA2G15 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
PLA2G15	NM_012320.4 linkuse as main transcript	c.115C>G	p.Pro39Ala	missense_variant	1/6	ENST00000219345.10
PLA2G15	NM_001363551.2 linkuse as main transcript	c.115C>G	p.Pro39Ala	missense_variant	1/6
PLA2G15	XM_011522979.3 linkuse as main transcript	c.115C>G	p.Pro39Ala	missense_variant	1/7
PLA2G15	XM_011522980.4 linkuse as main transcript	c.115C>G	p.Pro39Ala	missense_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLA2G15	ENST00000219345.10 linkuse as main transcript	c.115C>G	p.Pro39Ala	missense_variant	1/6	1	NM_012320.4	P1	Q8NCC3-1

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000296

AC:

AN:

202600

Hom.:

AF XY:

0.0000452

AC XY:

AN XY:

110700

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000129

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:

0.0000218

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000175

AC:

AN:

1431698

Hom.:

Cov.:

AF XY:

0.0000183

AC XY:

AN XY:

711242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000949

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000120

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000154

Gnomad4 OTH exome

AF:

0.0000504

GnomAD4 genome

AF:

0.0000986

AC:

AN:

152106

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000851

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000117

ExAC

AF:

0.00000831

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

Feb 16, 2023

The c.115C>G (p.P39A) alteration is located in exon 1 (coding exon 1) of the PLA2G15 gene. This alteration results from a C to G substitution at nucleotide position 115, causing the proline (P) at amino acid position 39 to be replaced by an alanine (A). 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

0.18

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Pathogenic

0.22

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.37

.;T;D;T;.;T;T

Eigen

Uncertain

0.38

Eigen_PC

Benign

0.20

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.50

T;T;T;T;T;T;T

M_CAP

Pathogenic

0.60

MetaRNN

Uncertain

0.67

D;D;D;D;D;D;D

MetaSVM

Pathogenic

0.92

MutationAssessor

Benign

0.0

N;.;N;.;.;.;.

MutationTaster

Benign

1.0

D;D;N;N

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.020

N;D;D;D;D;N;D

REVEL

Pathogenic

0.69

Sift

Pathogenic

0.0

D;D;D;D;D;T;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D;D

Polyphen

1.0

.;.;D;.;D;D;.

Vest4

0.31

MutPred

0.79

Loss of catalytic residue at P38 (P = 0.0131);Loss of catalytic residue at P38 (P = 0.0131);Loss of catalytic residue at P38 (P = 0.0131);Loss of catalytic residue at P38 (P = 0.0131);Loss of catalytic residue at P38 (P = 0.0131);Loss of catalytic residue at P38 (P = 0.0131);Loss of catalytic residue at P38 (P = 0.0131);

MVP

0.94

MPC

0.46

ClinPred

0.21

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.86

gMVP

0.86

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