22-38169411-G-T

Position:

• chr22-38169411-G-T

Variant summary

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

The ENST00000332509.8(PLA2G6):​c.16C>A​(p.Arg6Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. R6C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLA2G6 ENST00000332509.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.62

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/exons	MANE	Protein	UniProt
PLA2G6	NM_003560.4	c.16C>A	p.Arg6Ser	missense_variant	2/17	ENST00000332509.8	NP_003551.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLA2G6	ENST00000332509.8	c.16C>A	p.Arg6Ser	missense_variant	2/17	1	NM_003560.4	ENSP00000333142	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;.;.;.;.;T;T;T;.;T
Eigen	Benign	0.00063
Eigen_PC	Benign	0.046
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.95	D;D;.;D;D;.;.;D;D;D
M_CAP	Uncertain	0.23	D
MetaRNN	Uncertain	0.48	T;T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Uncertain	2.4	M;M;M;.;.;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;N;N
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.6	N;N;N;N;N;D;D;D;D;.
REVEL	Uncertain	0.30
Sift	Benign	0.11	T;T;T;D;D;D;D;D;D;.
Sift4G	Benign	0.16	T;T;T;T;D;T;T;T;.;.
Polyphen		0.31	B;D;D;.;.;.;.;.;.;.
Vest4		0.71
MutPred		0.46		Loss of MoRF binding (P = 6e-04);Loss of MoRF binding (P = 6e-04);Loss of MoRF binding (P = 6e-04);Loss of MoRF binding (P = 6e-04);Loss of MoRF binding (P = 6e-04);Loss of MoRF binding (P = 6e-04);Loss of MoRF binding (P = 6e-04);Loss of MoRF binding (P = 6e-04);Loss of MoRF binding (P = 6e-04);Loss of MoRF binding (P = 6e-04);
MVP		0.84
MPC		0.73
ClinPred		0.94	D
GERP RS		3.6
Varity_R		0.20
gMVP		0.77

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: rs143250889; hg19: chr22-38565418;