rs137883169

Variant names:

• chr6-46704657-T-C
• rs137883169
• NM_005084.4:c.1229A>G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_005084.4(PLA2G7):​c.1229A>G​(p.Glu410Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000235 in 1,577,572 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: PLA2G7 NM_005084.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.26
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.29193914).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G7	NM_005084.4	c.1229A>G	p.Glu410Gly	missense_variant	Exon 12 of 12	ENST00000274793.12	NP_005075.3
PLA2G7	NM_001168357.2	c.1229A>G	p.Glu410Gly	missense_variant	Exon 12 of 12		NP_001161829.1
PLA2G7	XM_005249408.5	c.1229A>G	p.Glu410Gly	missense_variant	Exon 12 of 12		XP_005249465.1
PLA2G7	XM_047419359.1	c.1094A>G	p.Glu365Gly	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	c.1229A>G	p.Glu410Gly	missense_variant	Exon 12 of 12	1	NM_005084.4	ENSP00000274793.7
PLA2G7	ENST00000537365.1	c.1229A>G	p.Glu410Gly	missense_variant	Exon 12 of 12	1		ENSP00000445666.1

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152186 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000289

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

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

GnomAD2 exomes AF: 0.0000518 AC: 13 AN: 250948 AF XY: 0.0000147

Gnomad AFR exome AF: 0.000678

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000161 AC: 23 AN: 1425268 Hom.: 0 Cov.: 27 AF XY: 0.0000183 AC XY: 13 AN XY: 711562

African (AFR) AF: 0.000517 AC: 17 AN: 32904

American (AMR) AF: 0.0000224 AC: 1 AN: 44584

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25934

East Asian (EAS) AF: 0.00 AC: 0 AN: 39442

South Asian (SAS) AF: 0.00 AC: 0 AN: 85610

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53376

Middle Eastern (MID) AF: 0.000350 AC: 2 AN: 5714

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078546

Other (OTH) AF: 0.0000507 AC: 3 AN: 59158

GnomAD4 genome AF: 0.0000919 AC: 14 AN: 152304 Hom.: 0 Cov.: 31 AF XY: 0.000107 AC XY: 8 AN XY: 74476

African (AFR) AF: 0.000289 AC: 12 AN: 41574

American (AMR) AF: 0.000131 AC: 2 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000778 Hom.: 1

Bravo AF: 0.000136

ESP6500AA AF: 0.00114 AC: 5

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000577 AC: 7

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1229A>G (p.E410G) alteration is located in exon 12 (coding exon 11) of the PLA2G7 gene. This alteration results from a A to G substitution at nucleotide position 1229, causing the glutamic acid (E) at amino acid position 410 to be replaced by a glycine (G). 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	Benign	0.12
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T;T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.86	.;D
M_CAP	Benign	0.061	D
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.9	M;M
PhyloP100		7.3
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-3.9	D;D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.96	D;D
Vest4		0.25
MVP		0.72
MPC		0.017
ClinPred		0.74	D
GERP RS		5.5
Varity_R		0.75
gMVP		0.58
Mutation Taster		=70/30	polymorphism

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

Other links and lift over

dbSNP: rs137883169; hg19: chr6-46672394;