rs121434634

chr1-186894164-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PP3_Strong PP5

The NM_024420.3(PLA2G4A):c.331T>C(p.Ser111Pro) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PLA2G4A NM_024420.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.79

Genes affected

PLA2G4A (HGNC:9035): (phospholipase A2 group IVA) This gene encodes a member of the cytosolic phospholipase A2 group IV family. The enzyme catalyzes the hydrolysis of membrane phospholipids to release arachidonic acid which is subsequently metabolized into eicosanoids. Eicosanoids, including prostaglandins and leukotrienes, are lipid-based cellular hormones that regulate hemodynamics, inflammatory responses, and other intracellular pathways. The hydrolysis reaction also produces lysophospholipids that are converted into platelet-activating factor. The enzyme is activated by increased intracellular Ca(2+) levels and phosphorylation, resulting in its translocation from the cytosol and nucleus to perinuclear membrane vesicles. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.968
• PP5: Variant 1-186894164-T-C is Pathogenic according to our data. Variant chr1-186894164-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 9079.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLA2G4A	NM_024420.3	c.331T>C	p.Ser111Pro	missense_variant	5/18	ENST00000367466.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLA2G4A	ENST00000367466.4	c.331T>C	p.Ser111Pro	missense_variant	5/18	1	NM_024420.3	P1
PLA2G4A	ENST00000466600.1	n.400T>C		non_coding_transcript_exon_variant	4/7	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1356400 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 680922

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Cytosolic phospholipase-A2 alpha deficiency associated bleeding disorder Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 01, 2008

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
Cadd	Benign	23
Dann	Uncertain	0.99
DEOGEN2	Uncertain	0.45	T
Eigen	Benign	0.058
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.034	D
MetaRNN	Pathogenic	0.97	D
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.9	M
MutationTaster	Benign	0.10	A;A
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.38
Sift	Benign	0.096	T
Sift4G	Benign	0.24	T
Polyphen		0.43	B
Vest4		0.83
MutPred		0.80		Gain of catalytic residue at M112 (P = 0.0317);
MVP		0.88
MPC		0.69
ClinPred		0.86	D
GERP RS		5.7
Varity_R		0.89
gMVP		0.73

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

LitVar

Other links and lift over

dbSNP: rs121434634; hg19: chr1-186863296;