22-38169318-G-C

Position:

• chr22-38169318-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003560.4(PLA2G6):​c.109C>G​(p.Arg37Gly) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLA2G6 NM_003560.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.88

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2150079).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLA2G6	NM_003560.4	c.109C>G	p.Arg37Gly	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.109C>G	p.Arg37Gly	missense_variant	2/17	1	NM_003560.4	ENSP00000333142.3

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	Benign	0.17
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T;.;.;.;.;T;T;T;.;T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.16	N
LIST_S2	Uncertain	0.88	D;D;.;D;D;.;.;D;D;D
M_CAP	Uncertain	0.098	D
MetaRNN	Benign	0.22	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	1.9	L;L;L;.;.;.;.;.;.;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.8	N;N;N;N;N;D;D;D;D;.
REVEL	Benign	0.28
Sift	Benign	0.56	T;T;T;T;T;T;T;T;T;.
Sift4G	Benign	0.45	T;T;T;T;T;D;D;D;.;.
Polyphen		0.30	B;D;D;.;.;.;.;.;.;.
Vest4		0.54
MutPred		0.52		Loss of stability (P = 0.072);Loss of stability (P = 0.072);Loss of stability (P = 0.072);Loss of stability (P = 0.072);Loss of stability (P = 0.072);Loss of stability (P = 0.072);Loss of stability (P = 0.072);Loss of stability (P = 0.072);Loss of stability (P = 0.072);Loss of stability (P = 0.072);
MVP		0.81
MPC		0.39
ClinPred		0.32	T
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.54

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: rs200075782; hg19: chr22-38565325;