11-63598127-G-A

Variant summary

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

The NM_001128203.2(PLAAT3):​c.52C>T​(p.Arg18Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000806 in 1,613,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

PLAAT3
NM_001128203.2 missense

Scores

11
4
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.82
Variant links:
Genes affected
PLAAT3 (HGNC:17825): (phospholipase A and acyltransferase 3) Enables N-acyltransferase activity; phospholipase A1 activity; and phospholipase A2 activity. Involved in N-acylphosphatidylethanolamine metabolic process. Predicted to be located in several cellular components, including lysosome; nuclear envelope; and peroxisome. Predicted to be active in cytoplasm. Biomarker of seminoma. [provided by Alliance of Genome Resources, Apr 2022]

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, 0.942

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PLAAT3NM_001128203.2 linkuse as main transcriptc.52C>T p.Arg18Cys missense_variant 3/5 ENST00000415826.3 NP_001121675.1 P53816A0A024R561
PLAAT3NM_007069.3 linkuse as main transcriptc.52C>T p.Arg18Cys missense_variant 2/4 NP_009000.2 P53816A0A024R561
PLAAT3XM_011544741.2 linkuse as main transcriptc.97C>T p.Arg33Cys missense_variant 2/4 XP_011543043.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PLAAT3ENST00000415826.3 linkuse as main transcriptc.52C>T p.Arg18Cys missense_variant 3/52 NM_001128203.2 ENSP00000389124.1 P53816

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152186
Hom.:
0
Cov.:
32
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
251466
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135912
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:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000821
AC:
12
AN:
1461706
Hom.:
0
Cov.:
30
AF XY:
0.00000825
AC XY:
6
AN XY:
727176
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.000115
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152186
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74338
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 GeneticsSep 20, 2024The c.52C>T (p.R18C) alteration is located in exon 2 (coding exon 2) of the PLA2G16 gene. This alteration results from a C to T substitution at nucleotide position 52, causing the arginine (R) at amino acid position 18 to be replaced by a cysteine (C). 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
0.76
BayesDel_addAF
Pathogenic
0.22
D
BayesDel_noAF
Pathogenic
0.18
CADD
Pathogenic
31
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.21
T;.;T
Eigen
Pathogenic
0.86
Eigen_PC
Pathogenic
0.76
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Pathogenic
0.98
.;D;D
M_CAP
Benign
0.036
D
MetaRNN
Pathogenic
0.94
D;D;D
MetaSVM
Uncertain
-0.045
T
PrimateAI
Uncertain
0.59
T
PROVEAN
Pathogenic
-6.1
D;.;D
REVEL
Uncertain
0.52
Sift
Pathogenic
0.0
D;.;D
Sift4G
Pathogenic
0.0
D;.;D
Polyphen
1.0
D;.;D
Vest4
0.93
MutPred
0.83
Loss of MoRF binding (P = 0.0794);.;Loss of MoRF binding (P = 0.0794);
MVP
0.81
MPC
0.93
ClinPred
0.99
D
GERP RS
6.0
Varity_R
0.76
gMVP
0.81

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.25
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.25
Position offset: -14
DS_AL_spliceai
0.22
Position offset: 36

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: rs761259464; hg19: chr11-63365599; API