15-42068932-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_178034.4(PLA2G4D):​c.2240G>A​(p.Arg747His) variant causes a missense change. The variant allele was found at a frequency of 0.00000994 in 1,609,524 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R747G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

PLA2G4D
NM_178034.4 missense

Scores

5
4
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.82
Variant links:
Genes affected
PLA2G4D (HGNC:30038): (phospholipase A2 group IVD) The phospholipase A2 enzyme family, including PLA2G4D, catalyze the hydrolysis of glycerophospholipids at the sn-2 position and then liberate free fatty acids and lysophospholipids (Chiba et al., 2004 [PubMed 14709560]).[supplied by OMIM, Jun 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.42057037).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PLA2G4DNM_178034.4 linkc.2240G>A p.Arg747His missense_variant 20/20 ENST00000290472.4 NP_828848.3 Q86XP0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PLA2G4DENST00000290472.4 linkc.2240G>A p.Arg747His missense_variant 20/201 NM_178034.4 ENSP00000290472.3 Q86XP0-1
PLA2G4DENST00000560932.1 linkn.1393G>A non_coding_transcript_exon_variant 5/51

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152158
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000425
AC:
1
AN:
235550
Hom.:
0
AF XY:
0.00000779
AC XY:
1
AN XY:
128388
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:
0.0000338
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000961
AC:
14
AN:
1457366
Hom.:
0
Cov.:
31
AF XY:
0.0000138
AC XY:
10
AN XY:
724770
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000234
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000900
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152158
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74332
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000540
Hom.:
0
Bravo
AF:
0.0000264

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 submitterclinical testingAmbry GeneticsJan 03, 2022The c.2240G>A (p.R747H) alteration is located in exon 20 (coding exon 20) of the PLA2G4D gene. This alteration results from a G to A substitution at nucleotide position 2240, causing the arginine (R) at amino acid position 747 to be replaced by a histidine (H). 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
0.23
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.33
CADD
Uncertain
24
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.27
T
Eigen
Uncertain
0.63
Eigen_PC
Uncertain
0.50
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.91
D
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.42
T
MetaSVM
Benign
-0.93
T
MutationAssessor
Pathogenic
3.5
M
PrimateAI
Benign
0.40
T
PROVEAN
Pathogenic
-4.9
D
REVEL
Benign
0.22
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.18
MutPred
0.57
Loss of phosphorylation at S748 (P = 0.1079);
MVP
0.72
MPC
0.31
ClinPred
0.99
D
GERP RS
4.7
Varity_R
0.84
gMVP
0.67

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs1373378653; hg19: chr15-42361130; COSMIC: COSV51820071; API