Variant 16-68245518-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_012320.4(PLA2G15):c.92C>T(p.Ala31Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000303 in 1,595,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00029 ( 0 hom. )

Consequence

PLA2G15
NM_012320.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.521

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.007904679).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PLA2G15	NM_012320.4 linkuse as main transcript	c.92C>T	p.Ala31Val	missense_variant	1/6	ENST00000219345.10
PLA2G15	NM_001363551.2 linkuse as main transcript	c.92C>T	p.Ala31Val	missense_variant	1/6
PLA2G15	XM_011522979.3 linkuse as main transcript	c.92C>T	p.Ala31Val	missense_variant	1/7
PLA2G15	XM_011522980.4 linkuse as main transcript	c.92C>T	p.Ala31Val	missense_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLA2G15	ENST00000219345.10 linkuse as main transcript	c.92C>T	p.Ala31Val	missense_variant	1/6	1	NM_012320.4	P1	Q8NCC3-1

Frequencies

GnomAD3 genomes

AF:

0.000388

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.00836

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000471

AC:

104

AN:

220894

Hom.:

AF XY:

0.000414

AC XY:

AN XY:

120830

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000672

Gnomad ASJ exome

AF:

0.00608

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000352

Gnomad FIN exome

AF:

0.000151

Gnomad NFE exome

AF:

0.000159

Gnomad OTH exome

AF:

0.000902

GnomAD4 exome

AF:

0.000294

AC:

425

AN:

1443734

Hom.:

Cov.:

AF XY:

0.000287

AC XY:

206

AN XY:

718082

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000619

Gnomad4 ASJ exome

AF:

0.00738

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000236

Gnomad4 FIN exome

AF:

0.0000903

Gnomad4 NFE exome

AF:

0.000148

Gnomad4 OTH exome

AF:

0.000534

GnomAD4 genome

AF:

0.000388

AC:

AN:

152146

Hom.:

Cov.:

AF XY:

0.000471

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000916

Gnomad4 ASJ

AF:

0.00836

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000480

Hom.:

Bravo

AF:

0.000521

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000323

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

Jul 14, 2021

The c.92C>T (p.A31V) alteration is located in exon 1 (coding exon 1) of the PLA2G15 gene. This alteration results from a C to T substitution at nucleotide position 92, causing the alanine (A) at amino acid position 31 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

0.084

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.010

.;T;T;T;.;T;T

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.55

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

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.0079

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

MetaSVM

Uncertain

0.45

MutationAssessor

Benign

0.0

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

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.42

N;N;N;N;N;N;N

REVEL

Benign

0.27

Sift

Pathogenic

0.0

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

Sift4G

Uncertain

0.025

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

Polyphen

0.20, 0.57

.;.;B;.;P;P;.

Vest4

0.21

MVP

0.37

MPC

0.73

ClinPred

0.097

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.086

gMVP

0.46

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