chr15-41840572-G-A

Position:

chr15-41840572-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001114633.2(PLA2G4B):c.131G>A(p.Ser44Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000452 in 1,613,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

PLA2G4B
NM_001114633.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.15

Variant links:

Genes affected

PLA2G4B (HGNC:9036): (phospholipase A2 group IVB) This gene encodes a member of the cytosolic phospholipase A2 protein family. Phospholipase A2 enzymes hydrolyze the sn-2 bond of phospholipids, releasing lysophospholipids and fatty acids. This enzyme may be associated with mitochondria and early endosomes. Most tissues also express read-through transcripts from the upstream gene into this gene, some of which may encode fusion proteins combining the N-terminus of the upstream gene including its JmjC domain with the almost complete coding region of this gene, including the C2 and cytoplasmic phospholipase A2 domains. [provided by RefSeq, Jul 2008]

PLA2G4B links:

JMJD7-PLA2G4B (HGNC:):

JMJD7-PLA2G4B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PLA2G4B	NM_001114633.2 linkuse as main transcript	c.131G>A	p.Ser44Asn	missense_variant	3/20	ENST00000458483.4
JMJD7-PLA2G4B	NM_005090.4 linkuse as main transcript	c.824G>A	p.Ser275Asn	missense_variant	8/25
JMJD7-PLA2G4B	NM_001198588.2 linkuse as main transcript	c.824G>A	p.Ser275Asn	missense_variant	8/24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLA2G4B	ENST00000458483.4 linkuse as main transcript	c.131G>A	p.Ser44Asn	missense_variant	3/20	2	NM_001114633.2	P1	P0C869-1
PLA2G4B	ENST00000452633.5 linkuse as main transcript	c.131G>A	p.Ser44Asn	missense_variant	4/21	5		P1	P0C869-1
PLA2G4B	ENST00000461382.5 linkuse as main transcript	n.232G>A		non_coding_transcript_exon_variant	3/10	2

Frequencies

GnomAD3 genomes

AF:

0.000302

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000604

AC:

AN:

248354

Hom.:

AF XY:

0.0000595

AC XY:

AN XY:

134496

show subpopulations

Gnomad AFR exome

AF:

0.000863

Gnomad AMR exome

AF:

0.0000289

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000185

AC:

AN:

1461632

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727098

show subpopulations

Gnomad4 AFR exome

AF:

0.000717

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.000302

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.000390

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.00106

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000493

Hom.:

Bravo

AF:

0.000317

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000988

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

Jul 20, 2022

The c.824G>A (p.S275N) alteration is located in exon 8 (coding exon 8) of the JMJD7-PLA2G4B gene. This alteration results from a G to A substitution at nucleotide position 824, causing the serine (S) at amino acid position 275 to be replaced by an asparagine (N). 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

0.16

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.44

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.012

.;.;T;T

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.27

T;T;.;T

M_CAP

Benign

0.035

MetaRNN

Benign

0.045

T;T;T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

0.83

.;.;L;L

MutationTaster

Benign

0.94

N;N;N;N

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.57

N;N;N;N

REVEL

Benign

0.12

Sift

Benign

0.42

T;T;T;T

Sift4G

Benign

0.51

T;T;T;T

Polyphen

0.99

.;.;D;D

Vest4

0.46

MVP

0.38

MPC

0.026

ClinPred

0.045

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.060

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.47

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.47

Position offset: 7

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