19-48067815-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003706.3(PLA2G4C):​c.1078A>C​(p.Thr360Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0983 in 1,610,696 control chromosomes in the GnomAD database, including 9,094 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: š‘“ 0.13 ( 1579 hom., cov: 31)
Exomes š‘“: 0.095 ( 7515 hom. )

Consequence

PLA2G4C
NM_003706.3 missense

Scores

3
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.33
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.004939705).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PLA2G4CNM_003706.3 linkc.1078A>C p.Thr360Pro missense_variant Exon 13 of 17 ENST00000599921.6 NP_003697.2 Q9UP65-1A0A024QZH0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PLA2G4CENST00000599921.6 linkc.1078A>C p.Thr360Pro missense_variant Exon 13 of 17 1 NM_003706.3 ENSP00000469473.1 Q9UP65-1
PLA2G4CENST00000595161.5 linkc.142A>C p.Thr48Pro missense_variant Exon 2 of 5 3 ENSP00000469528.1 M0QY18

Frequencies

GnomAD3 genomes
AF:
0.129
AC:
19636
AN:
151874
Hom.:
1579
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.229
Gnomad AMI
AF:
0.0910
Gnomad AMR
AF:
0.0876
Gnomad ASJ
AF:
0.0824
Gnomad EAS
AF:
0.000776
Gnomad SAS
AF:
0.0728
Gnomad FIN
AF:
0.110
Gnomad MID
AF:
0.0918
Gnomad NFE
AF:
0.0983
Gnomad OTH
AF:
0.108
GnomAD3 exomes
AF:
0.0904
AC:
22743
AN:
251470
Hom.:
1354
AF XY:
0.0893
AC XY:
12130
AN XY:
135902
show subpopulations
Gnomad AFR exome
AF:
0.232
Gnomad AMR exome
AF:
0.0555
Gnomad ASJ exome
AF:
0.0846
Gnomad EAS exome
AF:
0.000815
Gnomad SAS exome
AF:
0.0734
Gnomad FIN exome
AF:
0.104
Gnomad NFE exome
AF:
0.0983
Gnomad OTH exome
AF:
0.0830
GnomAD4 exome
AF:
0.0951
AC:
138760
AN:
1458704
Hom.:
7515
Cov.:
29
AF XY:
0.0948
AC XY:
68832
AN XY:
725838
show subpopulations
Gnomad4 AFR exome
AF:
0.232
Gnomad4 AMR exome
AF:
0.0590
Gnomad4 ASJ exome
AF:
0.0842
Gnomad4 EAS exome
AF:
0.000706
Gnomad4 SAS exome
AF:
0.0750
Gnomad4 FIN exome
AF:
0.105
Gnomad4 NFE exome
AF:
0.0974
Gnomad4 OTH exome
AF:
0.0921
GnomAD4 genome
AF:
0.129
AC:
19647
AN:
151992
Hom.:
1579
Cov.:
31
AF XY:
0.128
AC XY:
9510
AN XY:
74310
show subpopulations
Gnomad4 AFR
AF:
0.229
Gnomad4 AMR
AF:
0.0873
Gnomad4 ASJ
AF:
0.0824
Gnomad4 EAS
AF:
0.000778
Gnomad4 SAS
AF:
0.0731
Gnomad4 FIN
AF:
0.110
Gnomad4 NFE
AF:
0.0983
Gnomad4 OTH
AF:
0.107
Alfa
AF:
0.102
Hom.:
1604
Bravo
AF:
0.132
TwinsUK
AF:
0.0887
AC:
329
ALSPAC
AF:
0.0960
AC:
370
ESP6500AA
AF:
0.223
AC:
983
ESP6500EA
AF:
0.100
AC:
862
ExAC
AF:
0.0940
AC:
11416
Asia WGS
AF:
0.0500
AC:
176
AN:
3478
EpiCase
AF:
0.0994
EpiControl
AF:
0.0984

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.56
BayesDel_addAF
Benign
-0.68
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
16
DANN
Benign
0.80
DEOGEN2
Benign
0.018
.;.;T;T;.
Eigen
Benign
-0.38
Eigen_PC
Benign
-0.52
FATHMM_MKL
Benign
0.20
N
LIST_S2
Benign
0.38
T;T;T;T;T
MetaRNN
Benign
0.0049
T;T;T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
2.0
.;M;M;.;.
PrimateAI
Benign
0.39
T
PROVEAN
Uncertain
-3.1
.;D;.;.;.
REVEL
Benign
0.083
Sift
Benign
0.059
.;T;.;.;.
Sift4G
Uncertain
0.033
D;D;D;.;.
Polyphen
0.77
.;.;P;.;.
Vest4
0.073
MPC
0.55
ClinPred
0.044
T
GERP RS
1.7
Varity_R
0.28
gMVP
0.50

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.

Other links and lift over

dbSNP: rs11564620; hg19: chr19-48571072; COSMIC: COSV62786119; COSMIC: COSV62786119; API