11-63575024-G-A

Variant summary

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

The NM_001128203.2(PLAAT3):​c.410C>T​(p.Ala137Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000341 in 1,612,598 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A137P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000036 ( 1 hom. )

Consequence

PLAAT3
NM_001128203.2 missense

Scores

18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.665
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_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.018726975).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PLAAT3NM_001128203.2 linkuse as main transcriptc.410C>T p.Ala137Val missense_variant 5/5 ENST00000415826.3
PLAAT3NM_007069.3 linkuse as main transcriptc.410C>T p.Ala137Val missense_variant 4/4
PLAAT3XM_011544741.2 linkuse as main transcriptc.455C>T p.Ala152Val missense_variant 4/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PLAAT3ENST00000415826.3 linkuse as main transcriptc.410C>T p.Ala137Val missense_variant 5/52 NM_001128203.2 P1
PLAAT3ENST00000323646.9 linkuse as main transcriptc.410C>T p.Ala137Val missense_variant 4/41 P1
PLAAT3ENST00000394613.3 linkuse as main transcriptn.504C>T non_coding_transcript_exon_variant 4/41

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152250
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:
0.000385
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:
0.0000520
AC:
13
AN:
249928
Hom.:
0
AF XY:
0.0000444
AC XY:
6
AN XY:
135200
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000653
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000363
AC:
53
AN:
1460230
Hom.:
1
Cov.:
29
AF XY:
0.0000358
AC XY:
26
AN XY:
726526
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00118
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.0000663
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152368
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74514
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000227
ExAC
AF:
0.0000576
AC:
7
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

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 GeneticsDec 20, 2023The c.410C>T (p.A137V) alteration is located in exon 4 (coding exon 4) of the PLA2G16 gene. This alteration results from a C to T substitution at nucleotide position 410, causing the alanine (A) at amino acid position 137 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
0.12
BayesDel_addAF
Benign
-0.55
T
BayesDel_noAF
Benign
-0.66
CADD
Benign
1.6
DANN
Benign
0.41
DEOGEN2
Benign
0.017
T;.;T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.047
N
LIST_S2
Benign
0.49
.;T;T
M_CAP
Benign
0.0066
T
MetaRNN
Benign
0.019
T;T;T
MetaSVM
Benign
-0.99
T
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.27
T
PROVEAN
Benign
1.1
N;.;N
REVEL
Benign
0.048
Sift
Benign
0.63
T;.;T
Sift4G
Benign
0.41
T;.;T
Polyphen
0.0
B;.;B
Vest4
0.11
MVP
0.12
MPC
0.24
ClinPred
0.014
T
GERP RS
0.049
Varity_R
0.014
gMVP
0.20

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: rs199782544; hg19: chr11-63342496; API