11-63590278-C-A

Variant names:

• chr11-63590278-C-A
• NM_001128203.2:c.209G>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001128203.2(PLAAT3):​c.209G>T​(p.Gly70Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLAAT3 NM_001128203.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.71

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]

LOC105369335 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.873

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLAAT3	NM_001128203.2	c.209G>T	p.Gly70Val	missense_variant	Exon 4 of 5	ENST00000415826.3	NP_001121675.1
PLAAT3	NM_007069.3	c.209G>T	p.Gly70Val	missense_variant	Exon 3 of 4		NP_009000.2
PLAAT3	XM_011544741.2	c.254G>T	p.Gly85Val	missense_variant	Exon 3 of 4		XP_011543043.1
LOC105369335	XR_950179.3	n.*188C>A		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLAAT3	ENST00000415826.3	c.209G>T	p.Gly70Val	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

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 29, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.209G>T (p.G70V) alteration is located in exon 3 (coding exon 3) of the PLA2G16 gene. This alteration results from a G to T substitution at nucleotide position 209, causing the glycine (G) at amino acid position 70 to be replaced by a valine (V). 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	Pathogenic	0.70
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;.;T;T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.80	.;T;T;D
M_CAP	Benign	0.039	D
MetaRNN	Pathogenic	0.87	D;D;D;D
MetaSVM	Benign	-0.94	T
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-8.4	D;.;D;D
REVEL	Uncertain	0.50
Sift	Uncertain	0.0030	D;.;D;.
Sift4G	Uncertain	0.0020	D;.;D;.
Polyphen		1.0	D;.;D;.
Vest4		0.73
MutPred		0.66		Loss of helix (P = 0.0068);.;Loss of helix (P = 0.0068);.;
MVP		0.59
MPC		0.95
ClinPred		1.0	D
GERP RS		5.6
Varity_R		0.90
gMVP		0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-63357750;