Variant 4-109729670-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_030821.5(PLA2G12A):c.140C>T(p.Thr47Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000685 in 1,459,564 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

PLA2G12A
NM_030821.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.78

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15392411).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLA2G12A	NM_030821.5 linkuse as main transcript	c.140C>T	p.Thr47Met	missense_variant	1/4	ENST00000243501.10	NP_110448.2	Q9BZM1Q542Y6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PLA2G12A	ENST00000243501.10 linkuse as main transcript	c.140C>T	p.Thr47Met	missense_variant	1/4	1	NM_030821.5	ENSP00000243501.5	Q9BZM1
PLA2G12A	ENST00000502283.1 linkuse as main transcript	c.140C>T	p.Thr47Met	missense_variant	1/4	1		ENSP00000425274.1	A0A0C4DGC6
ENSG00000285330	ENST00000645635.1 linkuse as main transcript	c.1535-10911C>T		intron_variant				ENSP00000493607.1	A0A2R8Y3M9
PLA2G12A	ENST00000507961.1 linkuse as main transcript	n.140C>T		non_coding_transcript_exon_variant	1/3	2		ENSP00000424021.1	D6RBP5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000802

AC:

AN:

249470

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135232

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000685

AC:

AN:

1459564

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726084

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

May 13, 2024

The c.140C>T (p.T47M) alteration is located in exon 1 (coding exon 1) of the PLA2G12A gene. This alteration results from a C to T substitution at nucleotide position 140, causing the threonine (T) at amino acid position 47 to be replaced by a methionine (M). 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

0.096

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.034

T;T

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.82

T;T

M_CAP

Benign

0.0071

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;.

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.050

Sift

Benign

0.090

T;T

Sift4G

Benign

0.083

T;T

Polyphen

0.67

P;.

Vest4

0.15

MutPred

0.48

Gain of catalytic residue at T47 (P = 0.0174);Gain of catalytic residue at T47 (P = 0.0174);

MVP

0.32

MPC

0.079

ClinPred

0.30

GERP RS

2.1

Varity_R

0.035

gMVP

0.73

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