6-46708055-C-A

Variant names:

• chr6-46708055-C-A
• NM_005084.4:c.976G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005084.4(PLA2G7):​c.976G>T​(p.Ala326Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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: 0.00500
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08103967).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G7	NM_005084.4	c.976G>T	p.Ala326Ser	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.976G>T	p.Ala326Ser	missense_variant	Exon 10 of 12	1	NM_005084.4	ENSP00000274793.7
PLA2G7	ENST00000537365.1	c.976G>T	p.Ala326Ser	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

Jan 26, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.976G>T (p.A326S) alteration is located in exon 10 (coding exon 9) of the PLA2G7 gene. This alteration results from a G to T substitution at nucleotide position 976, causing the alanine (A) at amino acid position 326 to be replaced by a serine (S). 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	0.086
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	1.8
DANN	Benign	0.49
DEOGEN2	Benign	0.046	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.45	.;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.081	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.42	N;N
PhyloP100		0.0050
PrimateAI	Benign	0.20	T
PROVEAN	Benign	0.79	N;N
REVEL	Benign	0.039
Sift	Benign	0.56	T;T
Sift4G	Benign	0.71	T;T
Polyphen		0.0010	B;B
Vest4		0.12
MutPred		0.46		Gain of disorder (P = 0.1011);Gain of disorder (P = 0.1011);
MVP		0.19
MPC		0.0052
ClinPred		0.029	T
GERP RS		0.24
Varity_R		0.29
gMVP		0.26
Mutation Taster		=91/9	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: chr6-46675792;