chr11-63575028-C-G

Variant names:

• chr11-63575028-C-G
• rs751361809
• NM_001128203.2:c.406G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001128203.2(PLAAT3):​c.406G>C​(p.Ala136Pro) 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. A136T) 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: 0.227
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24263892).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLAAT3	NM_001128203.2	c.406G>C	p.Ala136Pro	missense_variant	Exon 5 of 5	ENST00000415826.3	NP_001121675.1
PLAAT3	NM_007069.3	c.406G>C	p.Ala136Pro	missense_variant	Exon 4 of 4		NP_009000.2
PLAAT3	XM_011544741.2	c.451G>C	p.Ala151Pro	missense_variant	Exon 4 of 4		XP_011543043.1
LOC105369335	XR_950179.3	n.-190C>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLAAT3	ENST00000415826.3	c.406G>C	p.Ala136Pro	missense_variant	Exon 5 of 5	2	NM_001128203.2	ENSP00000389124.1
PLAAT3	ENST00000323646.9	c.406G>C	p.Ala136Pro	missense_variant	Exon 4 of 4	1		ENSP00000320337.5
PLAAT3	ENST00000394613.3	n.500G>C		non_coding_transcript_exon_variant	Exon 4 of 4	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Benign	0.0082	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.084	T;.;T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.69	.;T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-0.98	T
PhyloP100		0.23
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.9	N;.;N
REVEL	Benign	0.27
Sift	Benign	0.085	T;.;T
Sift4G	Benign	0.070	T;.;T
Polyphen		0.98	D;.;D
Vest4		0.45
MutPred		0.46		Loss of MoRF binding (P = 0.187);.;Loss of MoRF binding (P = 0.187);
MVP		0.37
MPC		0.60
ClinPred		0.44	T
GERP RS		2.4
Varity_R		0.27
gMVP		0.64
Mutation Taster		=90/10	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: rs751361809; hg19: chr11-63342500;