NM_003560.4:c.1424G>T

Variant names:

• chr22-38126374-C-A
• rs139184008
• NM_003560.4:c.1424G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003560.4(PLA2G6):​c.1424G>T​(p.Arg475Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,460,100 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: PLA2G6 NM_003560.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.70

Genes affected

PLA2G6 (HGNC:9039): (phospholipase A2 group VI) The protein encoded by this gene is an A2 phospholipase, a class of enzyme that catalyzes the release of fatty acids from phospholipids. The encoded protein may play a role in phospholipid remodelling, arachidonic acid release, leukotriene and prostaglandin synthesis, fas-mediated apoptosis, and transmembrane ion flux in glucose-stimulated B-cells. Several transcript variants encoding multiple isoforms have been described, but the full-length nature of only three of them have been determined to date. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 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
PLA2G6	NM_003560.4	c.1424G>T	p.Arg475Leu	missense_variant	Exon 10 of 17	ENST00000332509.8	NP_003551.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G6	ENST00000332509.8	c.1424G>T	p.Arg475Leu	missense_variant	Exon 10 of 17	1	NM_003560.4	ENSP00000333142.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251106 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135820

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1460100 Hom.: 0 Cov.: 29 AF XY: 0.00000551 AC XY: 4 AN XY: 726480

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

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	0.26
BayesDel_addAF	Uncertain	0.062	T
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T;.;.
Eigen	Benign	0.067
Eigen_PC	Benign	0.10
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.79	T;D;.
M_CAP	Benign	0.050	D
MetaRNN	Uncertain	0.69	D;D;D
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.2	M;.;.
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-2.3	N;D;D
REVEL	Benign	0.29
Sift	Benign	0.31	T;T;T
Sift4G	Benign	0.50	T;T;T
Polyphen		0.48	P;D;D
Vest4		0.77
MutPred		0.52		Loss of disorder (P = 0.0493);.;.;
MVP		0.83
MPC		0.46
ClinPred		0.68	D
GERP RS		4.9
Varity_R		0.16
gMVP		0.60

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: rs139184008; hg19: chr22-38522381;