22-31137817-C-T

Position:

chr22-31137817-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_015715.5(PLA2G3):c.959G>A(p.Arg320His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

PLA2G3
NM_015715.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.898

Variant links:

Genes affected

PLA2G3 (HGNC:17934): (phospholipase A2 group III) This gene encodes a protein that belongs to the secreted phospholipase A2 family, whose members include the bee venom enzyme. The encoded enzyme functions in lipid metabolism and catalyzes the calcium-dependent hydrolysis of the sn-2 acyl bond of phospholipids to release arachidonic acid and lysophospholipids. This enzyme acts as a negative regulator of ciliogenesis, and may play a role in cancer development by stimulating tumor cell growth and angiogenesis. This gene is associated with oxidative stress, and polymorphisms in this gene are linked to risk for Alzheimer's disease. [provided by RefSeq, Apr 2014]

PLA2G3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.020532757).

BP6

Variant 22-31137817-C-T is Benign according to our data. Variant chr22-31137817-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2244700.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLA2G3	NM_015715.5 linkuse as main transcript	c.959G>A	p.Arg320His	missense_variant	4/7	ENST00000215885.4	NP_056530.2	Q9NZ20
PLA2G3	XM_011530204.2 linkuse as main transcript	c.416G>A	p.Arg139His	missense_variant	4/7		XP_011528506.1
PLA2G3	XM_011530205.2 linkuse as main transcript	c.416G>A	p.Arg139His	missense_variant	4/7		XP_011528507.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLA2G3	ENST00000215885.4 linkuse as main transcript	c.959G>A	p.Arg320His	missense_variant	4/7	1	NM_015715.5	ENSP00000215885.3		Q9NZ20

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152130

Hom.:

Cov.:

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:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000201

AC:

AN:

249004

Hom.:

AF XY:

0.00000742

AC XY:

AN XY:

134792

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461780

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152130

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000843

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 13, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.17

DANN

Benign

0.65

DEOGEN2

Benign

0.014

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0018

LIST_S2

Benign

0.24

M_CAP

Benign

0.0023

MetaRNN

Benign

0.021

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.23

PrimateAI

Benign

0.18

PROVEAN

Benign

0.42

REVEL

Benign

0.0010

Sift

Benign

0.48

Sift4G

Benign

0.35

Polyphen

0.0020

Vest4

0.052

MutPred

0.15

Loss of MoRF binding (P = 0.0283);

MVP

0.085

MPC

0.083

ClinPred

0.018

GERP RS

-6.2

Varity_R

0.015

gMVP

0.36

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over