16-68245529-G-A

Position:

chr16-68245529-G-A

Variant summary

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

The NM_012320.4(PLA2G15):c.103G>A(p.Gly35Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000022 in 1,590,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

PLA2G15
NM_012320.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.286

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:

PLA2G15 (HGNC:):

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=0.043177366).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLA2G15	NM_012320.4 linkuse as main transcript	c.103G>A	p.Gly35Arg	missense_variant	1/6	ENST00000219345.10	NP_036452.1	Q8NCC3-1
PLA2G15	NM_001363551.2 linkuse as main transcript	c.103G>A	p.Gly35Arg	missense_variant	1/6		NP_001350480.1
PLA2G15	XM_011522979.3 linkuse as main transcript	c.103G>A	p.Gly35Arg	missense_variant	1/7		XP_011521281.1
PLA2G15	XM_011522980.4 linkuse as main transcript	c.103G>A	p.Gly35Arg	missense_variant	1/7		XP_011521282.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLA2G15	ENST00000219345.10 linkuse as main transcript	c.103G>A	p.Gly35Arg	missense_variant	1/6	1	NM_012320.4	ENSP00000219345.5		Q8NCC3-1

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000381

AC:

AN:

210124

Hom.:

AF XY:

0.0000435

AC XY:

AN XY:

114834

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000157

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:

0.0000105

Gnomad OTH exome

AF:

0.000374

GnomAD4 exome

AF:

0.0000146

AC:

AN:

1438096

Hom.:

Cov.:

AF XY:

0.0000168

AC XY:

AN XY:

714852

show subpopulations

Gnomad4 AFR exome

AF:

0.0000304

Gnomad4 AMR exome

AF:

0.000303

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:

9.05e-7

Gnomad4 OTH exome

AF:

0.000101

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152108

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000916

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000355

ExAC

AF:

0.00000829

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

Oct 03, 2022

The c.103G>A (p.G35R) alteration is located in exon 1 (coding exon 1) of the PLA2G15 gene. This alteration results from a G to A substitution at nucleotide position 103, causing the glycine (G) at amino acid position 35 to be replaced by an arginine (R). 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

0.081

BayesDel_addAF

Uncertain

0.045

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.0094

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

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0047

LIST_S2

Benign

0.61

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

M_CAP

Benign

0.081

MetaRNN

Benign

0.043

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

MetaSVM

Uncertain

0.16

MutationAssessor

Benign

0.0

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

PrimateAI

Benign

0.46

PROVEAN

Benign

0.13

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

REVEL

Benign

0.26

Sift

Pathogenic

0.0

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

Sift4G

Uncertain

0.030

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

Polyphen

0.0010, 0.0020, 0.0080

.;.;B;.;B;B;.

Vest4

0.32

MutPred

0.35

Loss of relative solvent accessibility (P = 0.0404);Loss of relative solvent accessibility (P = 0.0404);Loss of relative solvent accessibility (P = 0.0404);Loss of relative solvent accessibility (P = 0.0404);Loss of relative solvent accessibility (P = 0.0404);Loss of relative solvent accessibility (P = 0.0404);Loss of relative solvent accessibility (P = 0.0404);

MVP

0.17

MPC

1.3

ClinPred

0.053

GERP RS

-0.17

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.41

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