Variant chr19-48048348-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003706.3(PLA2G4C):c.1621G>A(p.Ala541Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000123 in 1,598,226 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 1 hom. )

Consequence

PLA2G4C
NM_003706.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.512

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:

PLA2G4C (HGNC:):

PLA2G4C links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.038257897).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLA2G4C	NM_003706.3 linkuse as main transcript	c.1621G>A	p.Ala541Thr	missense_variant	17/17	ENST00000599921.6	NP_003697.2	Q9UP65-1A0A024QZH0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PLA2G4C	ENST00000599921.6 linkuse as main transcript	c.1621G>A	p.Ala541Thr	missense_variant	17/17	1	NM_003706.3	ENSP00000469473.1	Q9UP65-1
PLA2G4C	ENST00000594790.1 linkuse as main transcript	n.374G>A		non_coding_transcript_exon_variant	3/3	1
PLA2G4C	ENST00000599111.5 linkuse as main transcript	c.1651G>A	p.Ala551Thr	missense_variant	17/17	2		ENSP00000472546.1	Q9UP65-3
PLA2G4C	ENST00000354276 linkuse as main transcript	c.*80G>A		3_prime_UTR_variant	17/17	2		ENSP00000346228.2	Q9UP65-2

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000848

AC:

AN:

235822

Hom.:

AF XY:

0.0000936

AC XY:

AN XY:

128176

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000174

Gnomad OTH exome

AF:

0.000177

GnomAD4 exome

AF:

0.000127

AC:

184

AN:

1446106

Hom.:

Cov.:

AF XY:

0.000125

AC XY:

AN XY:

719404

show subpopulations

Gnomad4 AFR exome

AF:

0.0000308

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:

0.000160

Gnomad4 OTH exome

AF:

0.000100

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152120

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.0000966

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000173

Hom.:

Bravo

AF:

0.0000567

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.000115

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

Sep 14, 2022

The c.1621G>A (p.A541T) alteration is located in exon 17 (coding exon 16) of the PLA2G4C gene. This alteration results from a G to A substitution at nucleotide position 1621, causing the alanine (A) at amino acid position 541 to be replaced by a threonine (T). 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

0.086

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.69

CADD

Benign

1.4

DANN

Benign

0.80

DEOGEN2

Benign

0.00060

.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0026

LIST_S2

Benign

0.37

T;T

M_CAP

Benign

0.0029

MetaRNN

Benign

0.038

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.69

.;N

PrimateAI

Benign

0.41

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.0

.;B

Vest4

0.036

MutPred

0.36

.;Gain of catalytic residue at A541 (P = 0.1117);

MVP

0.048

MPC

0.093

ClinPred

0.028

GERP RS

-3.1

Varity_R

0.047

gMVP

0.30

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