Variant 4-109717607-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_030821.5(PLA2G12A):c.392G>T(p.Cys131Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,518 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

PLA2G12A
NM_030821.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.49

Variant links:

Genes affected

PLA2G12A (HGNC:18554): (phospholipase A2 group XIIA) Secreted phospholipase A2 (sPLA2) enzymes liberate arachidonic acid from phospholipids for production of eicosanoids and exert a variety of physiologic and pathologic effects. Group XII sPLA2s, such as PLA2G12A, have relatively low specific activity and are structurally and functionally distinct from other sPLA2s (Gelb et al., 2000 [PubMed 11031251]).[supplied by OMIM, Mar 2008]

PLA2G12A links:

ENSG00000285330 (HGNC:):

ENSG00000285330 links:

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ACMG classification

Classification made for transcript

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, 0.977

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLA2G12A	NM_030821.5 linkuse as main transcript	c.392G>T	p.Cys131Phe	missense_variant	3/4	ENST00000243501.10	NP_110448.2	Q9BZM1Q542Y6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLA2G12A	ENST00000243501.10 linkuse as main transcript	c.392G>T	p.Cys131Phe	missense_variant	3/4	1	NM_030821.5	ENSP00000243501.5		Q9BZM1
ENSG00000285330	ENST00000645635.1 linkuse as main transcript	c.1718G>T	p.Cys573Phe	missense_variant	14/15			ENSP00000493607.1		A0A2R8Y3M9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461518

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727084

show subpopulations

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:

0.00000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000377

Hom.:

Bravo

AF:

0.00000378

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 06, 2023

The c.392G>T (p.C131F) alteration is located in exon 3 (coding exon 3) of the PLA2G12A gene. This alteration results from a G to T substitution at nucleotide position 392, causing the cysteine (C) at amino acid position 131 to be replaced by a phenylalanine (F). 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

0.47

BayesDel_noAF

Pathogenic

0.43

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.47

T;T;.

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.78

T;T;T

M_CAP

Benign

0.041

MetaRNN

Pathogenic

0.98

D;D;D

MetaSVM

Uncertain

0.20

MutationAssessor

Pathogenic

3.3

M;.;.

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-11

D;D;.

REVEL

Pathogenic

0.91

Sift

Pathogenic

0.0

D;D;.

Sift4G

Pathogenic

0.0

D;D;.

Polyphen

1.0

D;.;.

Vest4

0.90

MutPred

0.89

Loss of catalytic residue at L132 (P = 0.012);.;.;

MVP

0.67

MPC

0.32

ClinPred

1.0

GERP RS

4.6

Varity_R

0.96

gMVP

0.94

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over