12-120326012-C-G

Variant names:

• chr12-120326012-C-G
• rs746790393
• NM_000928.3:c.43G>C

Variant summary

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

The NM_000928.3(PLA2G1B):​c.43G>C​(p.Ala15Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLA2G1B NM_000928.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.142

Genes affected

PLA2G1B (HGNC:9030): (phospholipase A2 group IB) This gene encodes a secreted member of the phospholipase A2 (PLA2) class of enzymes, which is produced by the pancreatic acinar cells. The encoded calcium-dependent enzyme catalyzes the hydrolysis of the sn-2 position of membrane glycerophospholipids to release arachidonic acid (AA) and lysophospholipids. AA is subsequently converted by downstream metabolic enzymes to several bioactive lipophilic compounds (eicosanoids), including prostaglandins (PGs) and leukotrienes (LTs). The enzyme may be involved in several physiological processes including cell contraction, cell proliferation and pathological response. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G1B	NM_000928.3	c.43G>C	p.Ala15Pro	missense_variant	Exon 2 of 4	ENST00000308366.9	NP_000919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G1B	ENST00000308366.9	c.43G>C	p.Ala15Pro	missense_variant	Exon 2 of 4	1	NM_000928.3	ENSP00000312286.4
PLA2G1B	ENST00000423423.3	c.43G>C	p.Ala15Pro	missense_variant	Exon 2 of 3	1		ENSP00000413594.3
PLA2G1B	ENST00000549767.1	c.-45G>C		5_prime_UTR_variant	Exon 1 of 3	2		ENSP00000447233.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.0034	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	14
DANN	Benign	0.96
DEOGEN2	Uncertain	0.77	D;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.48	T;T
M_CAP	Uncertain	0.097	D
MetaRNN	Uncertain	0.66	D;D
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.9	M;.
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-2.5	D;N
REVEL	Benign	0.20
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.018	D;D
Polyphen		0.56	P;P
Vest4		0.59
MutPred		0.64		Gain of catalytic residue at V12 (P = 2e-04);Gain of catalytic residue at V12 (P = 2e-04);
MVP		0.17
MPC		0.31
ClinPred		0.87	D
GERP RS		-6.6
Varity_R		0.46
gMVP		0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs746790393; hg19: chr12-120763815;