Genetic Variant PLAAT3:p.Ile150Met (chr11-63574984-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001128203.2(PLAAT3):c.450T>G(p.Ile150Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,888 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: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PLAAT3
NM_001128203.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.252

Publications

0 publications found

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]

PLAAT3 Gene-Disease associations (from GenCC):

lipodystrophy, familial partial, type 9
Inheritance: AR Classification: LIMITED Submitted by: G2P, Ambry Genetics

PLAAT3 links:

LOC105369335 (HGNC:):

LOC105369335 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26300418).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLAAT3	NM_001128203.2 link	c.450T>G	p.Ile150Met	missense_variant	Exon 5 of 5	ENST00000415826.3	NP_001121675.1	P53816A0A024R561
PLAAT3	NM_007069.3 link	c.450T>G	p.Ile150Met	missense_variant	Exon 4 of 4		NP_009000.2	P53816A0A024R561
PLAAT3	XM_011544741.2 link	c.495T>G	p.Ile165Met	missense_variant	Exon 4 of 4		XP_011543043.1
LOC105369335	XR_950179.3 link	n.-234A>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PLAAT3	ENST00000415826.3 link	c.450T>G	p.Ile150Met	missense_variant	Exon 5 of 5	2	NM_001128203.2	ENSP00000389124.1	P53816
PLAAT3	ENST00000323646.9 link	c.450T>G	p.Ile150Met	missense_variant	Exon 4 of 4	1		ENSP00000320337.5	P53816
PLAAT3	ENST00000394613.3 link	n.544T>G		non_coding_transcript_exon_variant	Exon 4 of 4	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460888

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726810

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33464

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111108

Other (OTH)

AF:

0.00

AC:

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 28, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.450T>G (p.I150M) alteration is located in exon 4 (coding exon 4) of the PLA2G16 gene. This alteration results from a T to G substitution at nucleotide position 450, causing the isoleucine (I) at amino acid position 150 to be replaced by a methionine (M). 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

0.087

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.031

T;.;T

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.72

.;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.26

T;T;T

MetaSVM

Benign

-0.97

PhyloP100

-0.25

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.90

N;.;N

REVEL

Benign

0.14

Sift

Uncertain

0.028

D;.;D

Sift4G

Benign

0.072

T;.;T

Polyphen

0.85

P;.;P

Vest4

0.39

MutPred

0.55

Gain of disorder (P = 0.0165);.;Gain of disorder (P = 0.0165);

MVP

0.34

MPC

0.44

ClinPred

0.65

GERP RS

-2.2

Varity_R

0.078

gMVP

0.27

Mutation Taster

=89/11

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over