6-46709361-C-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PM5PP3_Moderate

The NM_005084.4(PLA2G7):ā€‹c.835G>Cā€‹(p.Val279Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,544 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V279F) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

PLA2G7
NM_005084.4 missense

Scores

1
8
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.79
Variant links:
Genes affected
PLA2G7 (HGNC:9040): (phospholipase A2 group VII) The protein encoded by this gene is a secreted enzyme that catalyzes the degradation of platelet-activating factor to biologically inactive products. Defects in this gene are a cause of platelet-activating factor acetylhydrolase deficiency. Two transcript variants encoding the same protein have been found for this gene.[provided by RefSeq, Dec 2009]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM5
Other missense variant is known to change same aminoacid residue: Variant chr6-46709361-C-A is described in Lovd as [Pathogenic].
PP3
MetaRNN computational evidence supports a deleterious effect, 0.841

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PLA2G7NM_005084.4 linkuse as main transcriptc.835G>C p.Val279Leu missense_variant 9/12 ENST00000274793.12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PLA2G7ENST00000274793.12 linkuse as main transcriptc.835G>C p.Val279Leu missense_variant 9/121 NM_005084.4 P1
PLA2G7ENST00000537365.1 linkuse as main transcriptc.835G>C p.Val279Leu missense_variant 9/121 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.87e-7
AC:
1
AN:
1455544
Hom.:
0
Cov.:
27
AF XY:
0.00000138
AC XY:
1
AN XY:
724630
show subpopulations
Gnomad4 AFR exome
AF:
0.0000300
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.54
BayesDel_addAF
Uncertain
0.058
T
BayesDel_noAF
Benign
-0.15
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.19
T;T
Eigen
Uncertain
0.50
Eigen_PC
Uncertain
0.48
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.95
.;D
M_CAP
Benign
0.015
T
MetaRNN
Pathogenic
0.84
D;D
MetaSVM
Benign
-0.73
T
MutationAssessor
Uncertain
2.1
M;M
MutationTaster
Benign
1.0
D;D
PrimateAI
Benign
0.45
T
PROVEAN
Benign
-1.4
N;N
REVEL
Benign
0.22
Sift
Benign
0.034
D;D
Sift4G
Benign
0.15
T;T
Polyphen
0.99
D;D
Vest4
0.72
MutPred
0.71
Loss of phosphorylation at T282 (P = 0.1486);Loss of phosphorylation at T282 (P = 0.1486);
MVP
0.36
MPC
0.017
ClinPred
0.94
D
GERP RS
5.1
Varity_R
0.87
gMVP
0.81

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: rs76863441; hg19: chr6-46677098; API