Variant 4-109718742-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_030821.5(PLA2G12A):c.226C>T(p.Arg76Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 1,443,982 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: 0.000013 ( 0 hom. )

Consequence

PLA2G12A
NM_030821.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.14

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 Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.866

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLA2G12A	NM_030821.5 linkuse as main transcript	c.226C>T	p.Arg76Cys	missense_variant	2/4	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.226C>T	p.Arg76Cys	missense_variant	2/4	1	NM_030821.5	ENSP00000243501.5		Q9BZM1
ENSG00000285330	ENST00000645635.1 linkuse as main transcript	c.1552C>T	p.Arg518Cys	missense_variant	13/15			ENSP00000493607.1		A0A2R8Y3M9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000132

AC:

AN:

1443982

Hom.:

Cov.:

AF XY:

0.0000153

AC XY:

AN XY:

718826

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:

0.0000119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000136

Gnomad4 OTH exome

AF:

0.0000335

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

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

Jan 26, 2023

The c.226C>T (p.R76C) alteration is located in exon 2 (coding exon 2) of the PLA2G12A gene. This alteration results from a C to T substitution at nucleotide position 226, causing the arginine (R) at amino acid position 76 to be replaced by a cysteine (C). 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

0.84

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.15

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.21

T;T;.

Eigen

Pathogenic

0.92

Eigen_PC

Pathogenic

0.90

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Benign

0.0075

MetaRNN

Pathogenic

0.87

D;D;D

MetaSVM

Uncertain

0.047

MutationAssessor

Pathogenic

3.1

M;.;.

PrimateAI

Uncertain

0.66

PROVEAN

Pathogenic

-6.1

D;D;.

REVEL

Pathogenic

0.72

Sift

Uncertain

0.0010

D;D;.

Sift4G

Pathogenic

0.0

D;D;.

Polyphen

1.0

D;.;.

Vest4

0.81

MutPred

0.73

Gain of catalytic residue at P75 (P = 0.0074);Gain of catalytic residue at P75 (P = 0.0074);.;

MVP

0.66

MPC

0.15

ClinPred

1.0

GERP RS

5.7

Varity_R

0.55

gMVP

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.21

Position offset: 17

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