chr16-68259331-G-C

Position:

• chr16-68259331-G-C

Variant summary

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

The NM_012320.4(PLA2G15):​c.913G>C​(p.Glu305Gln) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLA2G15 NM_012320.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.08

Genes affected

PLA2G15 (HGNC:17163): (phospholipase A2 group XV) Lysophospholipases are enzymes that act on biological membranes to regulate the multifunctional lysophospholipids. The protein encoded by this gene hydrolyzes lysophosphatidylcholine to glycerophosphorylcholine and a free fatty acid. This enzyme is present in the plasma and thought to be associated with high-density lipoprotein. A later paper contradicts the function of this gene. It demonstrates that this gene encodes a lysosomal enzyme instead of a lysophospholipase and has both calcium-independent phospholipase A2 and transacylase activities. [provided by RefSeq, Jul 2008]

(HGNC:):

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=0.15365687).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLA2G15	NM_012320.4	c.913G>C	p.Glu305Gln	missense_variant	6/6	ENST00000219345.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLA2G15	ENST00000219345.10	c.913G>C	p.Glu305Gln	missense_variant	6/6	1	NM_012320.4	P1
	ENST00000563175.1	n.202+423C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 21, 2023

The c.913G>C (p.E305Q) alteration is located in exon 6 (coding exon 6) of the PLA2G15 gene. This alteration results from a G to C substitution at nucleotide position 913, causing the glutamic acid (E) at amino acid position 305 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Uncertain	0.079	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.58	.;D;D
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.88	D;D;D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Uncertain	0.14	D
MutationAssessor	Benign	1.9	.;L;.
MutationTaster	Benign	0.85	D;D;D;D
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.7	N;N;N
REVEL	Uncertain	0.30
Sift	Benign	0.11	T;T;T
Sift4G	Benign	0.14	T;T;T
Polyphen		0.034, 0.25	.;B;B
Vest4		0.21
MutPred		0.51		.;Gain of helix (P = 0.1736);.;
MVP		0.69
MPC		0.44
ClinPred		0.24	T
GERP RS		1.4
Varity_R		0.14
gMVP		0.84

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: chr16-68293234;