NM_001128203.2:c.254C>G

Variant names:

• chr11-63590233-G-C
• rs141685584
• NM_001128203.2:c.254C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001128203.2(PLAAT3):​c.254C>G​(p.Ser85Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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. S85L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLAAT3 NM_001128203.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.301
• Publications: 4 publications found

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

LOC105369335 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38772035).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLAAT3	NM_001128203.2	c.254C>G	p.Ser85Trp	missense_variant	Exon 4 of 5	ENST00000415826.3	NP_001121675.1
PLAAT3	NM_007069.3	c.254C>G	p.Ser85Trp	missense_variant	Exon 3 of 4		NP_009000.2
PLAAT3	XM_011544741.2	c.299C>G	p.Ser100Trp	missense_variant	Exon 3 of 4		XP_011543043.1
LOC105369335	XR_950179.3	n.*143G>C		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLAAT3	ENST00000415826.3	c.254C>G	p.Ser85Trp	missense_variant	Exon 4 of 5	2	NM_001128203.2	ENSP00000389124.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T;.;T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.096	N
LIST_S2	Benign	0.42	.;T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.39	T;T;T
MetaSVM	Benign	-1.0	T
PhyloP100		0.30
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-3.7	D;.;D
REVEL	Benign	0.034
Sift	Uncertain	0.016	D;.;D
Sift4G	Uncertain	0.014	D;.;D
Polyphen		0.95	P;.;P
Vest4		0.28
MutPred		0.28		Loss of disorder (P = 0.0034);.;Loss of disorder (P = 0.0034);
MVP		0.39
MPC		0.90
ClinPred		0.88	D
GERP RS		2.1
Varity_R		0.14
gMVP		0.35
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs141685584; hg19: chr11-63357705;