6-46711566-A-T

Variant names:

• chr6-46711566-A-T
• rs1805018
• NM_005084.4:c.593T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005084.4(PLA2G7):​c.593T>A​(p.Ile198Lys) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I198T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLA2G7 NM_005084.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.034219623).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005084.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G7	NM_005084.4	MANE Select	c.593T>A	p.Ile198Lys	missense	Exon 7 of 12	NP_005075.3
	PLA2G7	NM_001168357.2		c.593T>A	p.Ile198Lys	missense	Exon 7 of 12	NP_001161829.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G7	ENST00000274793.12	TSL:1 MANE Select	c.593T>A	p.Ile198Lys	missense	Exon 7 of 12	ENSP00000274793.7
	PLA2G7	ENST00000537365.1	TSL:1	c.593T>A	p.Ile198Lys	missense	Exon 7 of 12	ENSP00000445666.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.0080
DANN	Benign	0.48
DEOGEN2	Benign	0.041	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.28	N
PhyloP100		-1.1
PrimateAI	Benign	0.28	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.042
Sift	Benign	0.56	T
Sift4G	Benign	0.93	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.42		Loss of catalytic residue at I198 (P = 3e-04)
MVP		0.21
MPC		0.0039
ClinPred		0.023	T
GERP RS		-7.6
Varity_R		0.14
gMVP		0.50
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1805018; hg19: chr6-46679303;