chr6-46704623-G-T

Variant names:

• chr6-46704623-G-T
• NM_005084.4:c.1263C>A

Variant summary

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

The NM_005084.4(PLA2G7):​c.1263C>A​(p.Asn421Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,432,050 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.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: PLA2G7 NM_005084.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.341

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=0.37122896).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G7	NM_005084.4	c.1263C>A	p.Asn421Lys	missense_variant	Exon 12 of 12	ENST00000274793.12	NP_005075.3
PLA2G7	NM_001168357.2	c.1263C>A	p.Asn421Lys	missense_variant	Exon 12 of 12		NP_001161829.1
PLA2G7	XM_005249408.5	c.1263C>A	p.Asn421Lys	missense_variant	Exon 12 of 12		XP_005249465.1
PLA2G7	XM_047419359.1	c.1128C>A	p.Asn376Lys	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.1263C>A	p.Asn421Lys	missense_variant	Exon 12 of 12	1	NM_005084.4	ENSP00000274793.7
PLA2G7	ENST00000537365.1	c.1263C>A	p.Asn421Lys	missense_variant	Exon 12 of 12	1		ENSP00000445666.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1432050 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 714456

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: 9.22e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.11	T;T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.69	.;T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.37	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.7	M;M
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.18
Sift	Benign	0.10	T;T
Sift4G	Uncertain	0.043	D;D
Polyphen		0.99	D;D
Vest4		0.48
MutPred		0.47		Gain of ubiquitination at N421 (P = 0.0121);Gain of ubiquitination at N421 (P = 0.0121);
MVP		0.42
MPC		0.0070
ClinPred		0.65	D
GERP RS		0.087
Varity_R		0.49
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-46672360;