Variant 19-48053000-G-T 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_003706.3(PLA2G4C):c.1577C>A(p.Ala526Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,454,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PLA2G4C
NM_003706.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.161

Variant links:

Genes affected

PLA2G4C (HGNC:9037): (phospholipase A2 group IVC) This gene encodes a protein which is a member of the phospholipase A2 enzyme family which hydrolyzes glycerophospholipids to produce free fatty acids and lysophospholipids, both of which serve as precursors in the production of signaling molecules. The encoded protein has been shown to be a calcium-independent and membrane bound enzyme. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2009]

PLA2G4C 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=0.23018906).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLA2G4C	NM_003706.3 linkuse as main transcript	c.1577C>A	p.Ala526Asp	missense_variant	16/17	ENST00000599921.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLA2G4C	ENST00000599921.6 linkuse as main transcript	c.1577C>A	p.Ala526Asp	missense_variant	16/17	1	NM_003706.3	A2	Q9UP65-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000803

AC:

AN:

249202

Hom.:

AF XY:

0.00000742

AC XY:

AN XY:

134714

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1454596

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722370

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000181

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

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

Aug 02, 2021

The c.1577C>A (p.A526D) alteration is located in exon 16 (coding exon 15) of the PLA2G4C gene. This alteration results from a C to A substitution at nucleotide position 1577, causing the alanine (A) at amino acid position 526 to be replaced by an aspartic acid (D). 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

0.59

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0044

.;.;T

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.37

T;T;T

M_CAP

Benign

0.0058

MetaRNN

Benign

0.23

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

.;M;M

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-2.8

.;D;.

REVEL

Benign

0.21

Sift

Uncertain

0.012

.;D;.

Sift4G

Uncertain

0.010

D;D;D

Polyphen

1.0

.;.;D

Vest4

0.50

MutPred

0.50

.;Gain of loop (P = 0.0111);Gain of loop (P = 0.0111);

MVP

0.29

MPC

0.58

ClinPred

0.79

GERP RS

-2.0

Varity_R

0.29

gMVP

0.71

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