12-120325009-A-G

Position:

• chr12-120325009-A-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_000928.3(PLA2G1B):​c.247T>C​(p.Cys83Arg) variant causes a missense change involving the alteration of a conserved nucleotide. 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: PLA2G1B NM_000928.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.31

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.985

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLA2G1B	NM_000928.3	c.247T>C	p.Cys83Arg	missense_variant	3/4	ENST00000308366.9	NP_000919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLA2G1B	ENST00000308366.9	c.247T>C	p.Cys83Arg	missense_variant	3/4	1	NM_000928.3	ENSP00000312286.4
PLA2G1B	ENST00000423423.3	c.194+852T>C		intron_variant		1		ENSP00000413594.3
PLA2G1B	ENST00000549767.1	c.160T>C	p.Cys54Arg	missense_variant	2/3	2		ENSP00000447233.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Oct 13, 2023

The c.247T>C (p.C83R) alteration is located in exon 3 (coding exon 3) of the PLA2G1B gene. This alteration results from a T to C substitution at nucleotide position 247, causing the cysteine (C) at amino acid position 83 to be replaced by an arginine (R). 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	0.98
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.20
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.55	D;T
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.076	D
MetaRNN	Pathogenic	0.99	D;D
MetaSVM	Uncertain	-0.075	T
MutationAssessor	Pathogenic	4.9	H;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-11	D;D
REVEL	Pathogenic	0.81
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.88
MutPred		0.86		Gain of catalytic residue at F85 (P = 0.0201);.;
MVP		0.56
MPC		0.50
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.98
gMVP		0.98

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-120762812;