Genetic Variant PLA2G4D:p.Gln705Arg (chr15-42070025-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_178034.4(PLA2G4D):c.2114A>G(p.Gln705Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000953 in 1,363,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000095 ( 0 hom. )

Consequence

PLA2G4D
NM_178034.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.03

Publications

0 publications found

Variant links:

Genes affected

PLA2G4D (HGNC:30038): (phospholipase A2 group IVD) The phospholipase A2 enzyme family, including PLA2G4D, catalyze the hydrolysis of glycerophospholipids at the sn-2 position and then liberate free fatty acids and lysophospholipids (Chiba et al., 2004 [PubMed 14709560]).[supplied by OMIM, Jun 2009]

PLA2G4D links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11477965).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178034.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G4D	NM_178034.4	MANE Select	c.2114A>G	p.Gln705Arg	missense	Exon 19 of 20	NP_828848.3	Q86XP0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G4D	ENST00000290472.4	TSL:1 MANE Select	c.2114A>G	p.Gln705Arg	missense	Exon 19 of 20	ENSP00000290472.3	Q86XP0-1
	PLA2G4D	ENST00000560932.1	TSL:1	n.1267A>G		non_coding_transcript_exon	Exon 4 of 5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000162

AC:

AN:

123550

AF XY:

0.0000152

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:

0.0000669

Gnomad NFE exome

AF:

0.0000210

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000953

AC:

AN:

1363878

Hom.:

Cov.:

AF XY:

0.00000595

AC XY:

AN XY:

671924

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28778

American (AMR)

AF:

0.00

AC:

AN:

29840

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24152

East Asian (EAS)

AF:

0.00

AC:

AN:

31950

South Asian (SAS)

AF:

0.00

AC:

AN:

73718

European-Finnish (FIN)

AF:

0.0000409

AC:

AN:

48950

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5050

European-Non Finnish (NFE)

AF:

0.0000103

AC:

AN:

1064906

Other (OTH)

AF:

0.00

AC:

AN:

56534

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000198

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.015

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.21

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.66

M_CAP

Benign

0.0042

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

PhyloP100

3.0

PrimateAI

Benign

0.28

PROVEAN

Benign

-2.1

REVEL

Benign

0.049

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.010

Polyphen

0.29

Vest4

0.18

MutPred

0.44

Gain of phosphorylation at S703 (P = 0.0851)

MVP

0.51

MPC

0.069

ClinPred

0.37

GERP RS

4.0

Varity_R

0.32

gMVP

0.25

Mutation Taster

=85/15

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over