22-31136993-C-T

Position:

• chr22-31136993-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015715.5(PLA2G3):​c.1114G>A​(p.Glu372Lys) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PLA2G3 NM_015715.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.290

Genes affected

PLA2G3 (HGNC:17934): (phospholipase A2 group III) This gene encodes a protein that belongs to the secreted phospholipase A2 family, whose members include the bee venom enzyme. The encoded enzyme functions in lipid metabolism and catalyzes the calcium-dependent hydrolysis of the sn-2 acyl bond of phospholipids to release arachidonic acid and lysophospholipids. This enzyme acts as a negative regulator of ciliogenesis, and may play a role in cancer development by stimulating tumor cell growth and angiogenesis. This gene is associated with oxidative stress, and polymorphisms in this gene are linked to risk for Alzheimer's disease. [provided by RefSeq, Apr 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.074413806).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLA2G3	NM_015715.5	c.1114G>A	p.Glu372Lys	missense_variant	5/7	ENST00000215885.4	NP_056530.2
PLA2G3	XM_011530204.2	c.571G>A	p.Glu191Lys	missense_variant	5/7		XP_011528506.1
PLA2G3	XM_011530205.2	c.571G>A	p.Glu191Lys	missense_variant	5/7		XP_011528507.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLA2G3	ENST00000215885.4	c.1114G>A	p.Glu372Lys	missense_variant	5/7	1	NM_015715.5	ENSP00000215885.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 13, 2021

The c.1114G>A (p.E372K) alteration is located in exon 5 (coding exon 5) of the PLA2G3 gene. This alteration results from a G to A substitution at nucleotide position 1114, causing the glutamic acid (E) at amino acid position 372 to be replaced by a lysine (K). 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	Benign	0.078
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	6.8
DANN	Uncertain	0.98
DEOGEN2	Benign	0.033	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.8	L
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.053
Sift	Benign	0.057	T
Sift4G	Uncertain	0.030	D
Polyphen		0.0010	B
Vest4		0.22
MutPred		0.41		Gain of methylation at E372 (P = 0.0028);
MVP		0.22
MPC		0.078
ClinPred		0.049	T
GERP RS		-1.1
Varity_R		0.13
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr22-31532979;