chr6-46708041-T-A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_005084.4(PLA2G7):​c.990A>T​(p.Lys330Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000878 in 1,594,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000083 ( 0 hom. )

Consequence

PLA2G7
NM_005084.4 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.25

Publications

0 publications found
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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.1453462).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PLA2G7NM_005084.4 linkc.990A>T p.Lys330Asn missense_variant Exon 10 of 12 ENST00000274793.12 NP_005075.3 Q13093

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PLA2G7ENST00000274793.12 linkc.990A>T p.Lys330Asn missense_variant Exon 10 of 12 1 NM_005084.4 ENSP00000274793.7 Q13093
PLA2G7ENST00000537365.1 linkc.990A>T p.Lys330Asn missense_variant Exon 10 of 12 1 ENSP00000445666.1 Q13093

Frequencies

GnomAD3 genomes
AF:
0.000131
AC:
20
AN:
152202
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.00122
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.000108
AC:
27
AN:
250514
AF XY:
0.000126
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 FIN exome
AF:
0.000694
Gnomad NFE exome
AF:
0.0000884
Gnomad OTH exome
AF:
0.000329
GnomAD4 exome
AF:
0.0000832
AC:
120
AN:
1442630
Hom.:
0
Cov.:
27
AF XY:
0.0000960
AC XY:
69
AN XY:
719066
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33020
American (AMR)
AF:
0.00
AC:
0
AN:
44598
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25972
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39524
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85848
European-Finnish (FIN)
AF:
0.00105
AC:
56
AN:
53356
Middle Eastern (MID)
AF:
0.000701
AC:
4
AN:
5708
European-Non Finnish (NFE)
AF:
0.0000475
AC:
52
AN:
1094876
Other (OTH)
AF:
0.000134
AC:
8
AN:
59728
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.490
Heterozygous variant carriers
0
8
16
23
31
39
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.000131
AC:
20
AN:
152320
Hom.:
0
Cov.:
32
AF XY:
0.000188
AC XY:
14
AN XY:
74478
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41566
American (AMR)
AF:
0.00
AC:
0
AN:
15280
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5190
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4830
European-Finnish (FIN)
AF:
0.00122
AC:
13
AN:
10624
Middle Eastern (MID)
AF:
0.00340
AC:
1
AN:
294
European-Non Finnish (NFE)
AF:
0.0000882
AC:
6
AN:
68038
Other (OTH)
AF:
0.00
AC:
0
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.513
Heterozygous variant carriers
0
1
3
4
6
7
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.000131
Hom.:
0
Bravo
AF:
0.0000302
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.000124
AC:
15
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 25, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.990A>T (p.K330N) alteration is located in exon 10 (coding exon 9) of the PLA2G7 gene. This alteration results from a A to T substitution at nucleotide position 990, causing the lysine (K) at amino acid position 330 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
Uncertain
0.35
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.13
T;T
Eigen
Benign
0.17
Eigen_PC
Benign
0.13
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Benign
0.62
.;T
M_CAP
Benign
0.037
D
MetaRNN
Benign
0.15
T;T
MetaSVM
Benign
-0.90
T
MutationAssessor
Uncertain
2.3
M;M
PhyloP100
1.3
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-2.2
N;N
REVEL
Benign
0.27
Sift
Benign
0.094
T;T
Sift4G
Benign
0.34
T;T
Polyphen
0.99
D;D
Vest4
0.48
MutPred
0.52
Loss of methylation at K330 (P = 0.0176);Loss of methylation at K330 (P = 0.0176);
MVP
0.63
MPC
0.019
ClinPred
0.15
T
GERP RS
4.5
Varity_R
0.57
gMVP
0.62
Mutation Taster
=54/46
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs199551268; hg19: chr6-46675778; API