Genetic Variant NM_001128203.2:c.409G>A (chr11-63575025-C-T) – 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.409G>A(p.Ala137Thr) 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 1,460,078 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A137V) has been classified 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

Not reported in ClinVar

Conservation

PhyloP100: 1.84

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=0.10124731).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLAAT3	NM_001128203.2 link	c.409G>A	p.Ala137Thr	missense_variant	Exon 5 of 5	ENST00000415826.3	NP_001121675.1	P53816A0A024R561
PLAAT3	NM_007069.3 link	c.409G>A	p.Ala137Thr	missense_variant	Exon 4 of 4		NP_009000.2	P53816A0A024R561
PLAAT3	XM_011544741.2 link	c.454G>A	p.Ala152Thr	missense_variant	Exon 4 of 4		XP_011543043.1
LOC105369335	XR_950179.3 link	n.-193C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PLAAT3	ENST00000415826.3 link	c.409G>A	p.Ala137Thr	missense_variant	Exon 5 of 5	2	NM_001128203.2	ENSP00000389124.1	P53816
PLAAT3	ENST00000323646.9 link	c.409G>A	p.Ala137Thr	missense_variant	Exon 4 of 4	1		ENSP00000320337.5	P53816
PLAAT3	ENST00000394613.3 link	n.503G>A		non_coding_transcript_exon_variant	Exon 4 of 4	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460078

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726448

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33448

American (AMR)

AF:

0.00

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

86224

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53330

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

9.01e-7

AC:

AN:

1110448

Other (OTH)

AF:

0.00

AC:

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.032

T;.;T

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.45

.;T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.10

T;T;T

MetaSVM

Benign

-1.0

PhyloP100

1.8

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.64

N;.;N

REVEL

Benign

0.098

Sift

Benign

0.095

T;.;T

Sift4G

Benign

0.15

T;.;T

Polyphen

0.0090

B;.;B

Vest4

0.32

MutPred

0.44

Gain of glycosylation at A137 (P = 0.0566);.;Gain of glycosylation at A137 (P = 0.0566);

MVP

0.27

MPC

0.24

ClinPred

0.20

GERP RS

4.3

Varity_R

0.039

gMVP

0.19

Mutation Taster

=94/6

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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NM_001128203.2:c.409G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over