11-63590233-G-C

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).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128203.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLAAT3	NM_001128203.2	MANE Select	c.254C>G	p.Ser85Trp	missense	Exon 4 of 5	NP_001121675.1	P53816
	PLAAT3	NM_007069.3		c.254C>G	p.Ser85Trp	missense	Exon 3 of 4	NP_009000.2	P53816

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLAAT3	ENST00000415826.3	TSL:2 MANE Select	c.254C>G	p.Ser85Trp	missense	Exon 4 of 5	ENSP00000389124.1	P53816
	PLAAT3	ENST00000323646.9	TSL:1	c.254C>G	p.Ser85Trp	missense	Exon 3 of 4	ENSP00000320337.5	P53816
	PLAAT3	ENST00000394613.3	TSL:1	n.348C>G		non_coding_transcript_exon	Exon 3 of 4

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 v4.9

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
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.096	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.30
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.034
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.014	D
Polyphen		0.95	P
Vest4		0.28
MutPred		0.28		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;