chr6-46705206-A-T

Variant names:

• chr6-46705206-A-T
• rs1051931
• NM_005084.4:c.1136T>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005084.4(PLA2G7):​c.1136T>A​(p.Val379Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,456,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. V379A) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PLA2G7 NM_005084.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.99

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3277443).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G7	NM_005084.4	c.1136T>A	p.Val379Glu	missense_variant	Exon 11 of 12	ENST00000274793.12	NP_005075.3
PLA2G7	NM_001168357.2	c.1136T>A	p.Val379Glu	missense_variant	Exon 11 of 12		NP_001161829.1
PLA2G7	XM_005249408.5	c.1136T>A	p.Val379Glu	missense_variant	Exon 11 of 12		XP_005249465.1
PLA2G7	XM_047419359.1	c.1001T>A	p.Val334Glu	missense_variant	Exon 10 of 11		XP_047275315.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G7	ENST00000274793.12	c.1136T>A	p.Val379Glu	missense_variant	Exon 11 of 12	1	NM_005084.4	ENSP00000274793.7
PLA2G7	ENST00000537365.1	c.1136T>A	p.Val379Glu	missense_variant	Exon 11 of 12	1		ENSP00000445666.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456052 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 724740

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.023	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	23
DANN	Benign	0.87
DEOGEN2	Benign	0.074	T;T
Eigen	Benign	0.036
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.68	.;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;L
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.17
Sift	Benign	0.26	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.56	P;P
Vest4		0.19
MutPred		0.58		Gain of disorder (P = 0.002);Gain of disorder (P = 0.002);
MVP		0.54
MPC		0.0082
ClinPred		0.77	D
GERP RS		5.9
Varity_R		0.69
gMVP		0.64

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

LitVar

Other links and lift over

dbSNP: rs1051931; hg19: chr6-46672943;