Genetic Variant PLA2G7:p.Asn421Lys (chr6-46704623-G-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_005084.4(PLA2G7):c.1263C>A(p.Asn421Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,432,050 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N421N) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

PLA2G7
NM_005084.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.341

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]

PLA2G7 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37122896).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G7	NM_005084.4 link	c.1263C>A	p.Asn421Lys	missense_variant	Exon 12 of 12	ENST00000274793.12	NP_005075.3	Q13093
PLA2G7	NM_001168357.2 link	c.1263C>A	p.Asn421Lys	missense_variant	Exon 12 of 12		NP_001161829.1	Q13093
PLA2G7	XM_005249408.5 link	c.1263C>A	p.Asn421Lys	missense_variant	Exon 12 of 12		XP_005249465.1	Q13093
PLA2G7	XM_047419359.1 link	c.1128C>A	p.Asn376Lys	missense_variant	Exon 11 of 11		XP_047275315.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G7	ENST00000274793.12 link	c.1263C>A	p.Asn421Lys	missense_variant	Exon 12 of 12	1	NM_005084.4	ENSP00000274793.7		Q13093
PLA2G7	ENST00000537365.1 link	c.1263C>A	p.Asn421Lys	missense_variant	Exon 12 of 12	1		ENSP00000445666.1		Q13093

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.98e-7

AC:

AN:

1432050

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

714456

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33006

American (AMR)

AF:

0.00

AC:

AN:

44602

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25936

East Asian (EAS)

AF:

0.00

AC:

AN:

39524

South Asian (SAS)

AF:

0.00

AC:

AN:

85724

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53376

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5716

European-Non Finnish (NFE)

AF:

9.22e-7

AC:

AN:

1084788

Other (OTH)

AF:

0.00

AC:

AN:

59378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.11

T;T

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.69

.;T

M_CAP

Benign

0.0083

MetaRNN

Benign

0.37

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.7

M;M

PhyloP100

-0.34

PrimateAI

Benign

0.31

PROVEAN

Benign

-2.0

N;N

REVEL

Benign

0.18

Sift

Benign

0.10

T;T

Sift4G

Uncertain

0.043

D;D

Polyphen

0.99

D;D

Vest4

0.48

MutPred

0.47

Gain of ubiquitination at N421 (P = 0.0121);Gain of ubiquitination at N421 (P = 0.0121);

MVP

0.42

MPC

0.0070

ClinPred

0.65

GERP RS

0.087

Varity_R

0.49

gMVP

0.64

Mutation Taster

=94/6

polymorphism

(source)

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

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6-46704623-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over