16-68259499-G-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_012320.4(PLA2G15):​c.1081G>A​(p.Gly361Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

PLA2G15
NM_012320.4 missense

Scores

11
6
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.90
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.962

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PLA2G15NM_012320.4 linkuse as main transcriptc.1081G>A p.Gly361Ser missense_variant 6/6 ENST00000219345.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PLA2G15ENST00000219345.10 linkuse as main transcriptc.1081G>A p.Gly361Ser missense_variant 6/61 NM_012320.4 P1Q8NCC3-1
ENST00000563175.1 linkuse as main transcriptn.202+255C>T intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000799
AC:
2
AN:
250350
Hom.:
0
AF XY:
0.00000738
AC XY:
1
AN XY:
135452
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:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1460802
Hom.:
0
Cov.:
32
AF XY:
0.00000413
AC XY:
3
AN XY:
726762
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:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.0000165
AC:
2

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 submitterclinical testingAmbry GeneticsMar 23, 2022The c.1081G>A (p.G361S) alteration is located in exon 6 (coding exon 6) of the PLA2G15 gene. This alteration results from a G to A substitution at nucleotide position 1081, causing the glycine (G) at amino acid position 361 to be replaced by a serine (S). 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
0.31
BayesDel_addAF
Pathogenic
0.54
D
BayesDel_noAF
Pathogenic
0.55
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.94
.;D;D
Eigen
Pathogenic
0.96
Eigen_PC
Pathogenic
0.94
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.89
D;D;D
M_CAP
Pathogenic
0.52
D
MetaRNN
Pathogenic
0.96
D;D;D
MetaSVM
Pathogenic
1.1
D
MutationAssessor
Pathogenic
3.4
.;M;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.69
T
PROVEAN
Uncertain
-3.6
D;D;D
REVEL
Pathogenic
0.94
Sift
Uncertain
0.011
D;D;D
Sift4G
Uncertain
0.013
D;D;D
Polyphen
1.0, 0.95
.;D;P
Vest4
0.84
MutPred
0.85
.;Loss of ubiquitination at K366 (P = 0.1343);.;
MVP
0.97
MPC
1.2
ClinPred
0.96
D
GERP RS
5.8
Varity_R
0.59
gMVP
0.96

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.

Other links and lift over

dbSNP: rs760142209; hg19: chr16-68293402; API