6-46707995-T-G

Variant names:

• chr6-46707995-T-G
• NM_005084.4:c.1036A>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005084.4(PLA2G7):​c.1036A>C​(p.Ile346Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 13/22 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)
• Consequence: PLA2G7 NM_005084.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.91
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G7	NM_005084.4	c.1036A>C	p.Ile346Leu	missense_variant	Exon 10 of 12	ENST00000274793.12	NP_005075.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G7	ENST00000274793.12	c.1036A>C	p.Ile346Leu	missense_variant	Exon 10 of 12	1	NM_005084.4	ENSP00000274793.7
PLA2G7	ENST00000537365.1	c.1036A>C	p.Ile346Leu	missense_variant	Exon 10 of 12	1		ENSP00000445666.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 10, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1036A>C (p.I346L) alteration is located in exon 10 (coding exon 9) of the PLA2G7 gene. This alteration results from a A to C substitution at nucleotide position 1036, causing the isoleucine (I) at amino acid position 346 to be replaced by a leucine (L). 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	0.15
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;T
Eigen	Benign	0.062
Eigen_PC	Benign	0.082
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.76	.;T
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.48	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.7	L;L
PhyloP100		3.9
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.21
Sift	Uncertain	0.013	D;D
Sift4G	Benign	0.21	T;T
Polyphen		0.42	B;B
Vest4		0.53
MutPred		0.71		Gain of methylation at R347 (P = 0.1266);Gain of methylation at R347 (P = 0.1266);
MVP		0.25
MPC		0.012
ClinPred		0.89	D
GERP RS		1.7
Varity_R		0.72
gMVP		0.73
Mutation Taster		=64/36	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

hg19: chr6-46675732;