16-14672718-C-G

Variant names:

• chr16-14672718-C-G
• NM_003561.3:c.387G>C

Variant summary

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

The NM_003561.3(PLA2G10):​c.387G>C​(p.Leu129Phe) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLA2G10 NM_003561.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.351

Genes affected

PLA2G10 (HGNC:9029): (phospholipase A2 group X) This gene encodes a member of the phospholipase A2 family of proteins. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature enzyme. This calcium-dependent enzyme hydrolyzes glycerophospholipids to produce free fatty acids and lysophospholipids. In one example, this enzyme catalyzes the release of arachidonic acid from cell membrane phospholipids, thus playing a role in the production of various inflammatory lipid mediators, such as prostaglandins. The encoded protein may promote the survival of breast cancer cells through its role in lipid metabolism. [provided by RefSeq, Nov 2015]

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=0.39248323).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G10	NM_003561.3	c.387G>C	p.Leu129Phe	missense_variant	Exon 4 of 4	ENST00000438167.8	NP_003552.1
PLA2G10	XM_047434757.1	c.387G>C	p.Leu129Phe	missense_variant	Exon 5 of 5		XP_047290713.1
PLA2G10	NR_133651.1	n.847G>C		non_coding_transcript_exon_variant	Exon 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G10	ENST00000438167.8	c.387G>C	p.Leu129Phe	missense_variant	Exon 4 of 4	1	NM_003561.3	ENSP00000393847.4
PLA2G10	ENST00000567462.1	n.*110G>C		non_coding_transcript_exon_variant	Exon 5 of 5	3		ENSP00000456433.1
PLA2G10	ENST00000567462.1	n.*110G>C		3_prime_UTR_variant	Exon 5 of 5	3		ENSP00000456433.1

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

Sep 16, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.387G>C (p.L129F) alteration is located in exon 4 (coding exon 4) of the PLA2G10 gene. This alteration results from a G to C substitution at nucleotide position 387, causing the leucine (L) at amino acid position 129 to be replaced by a phenylalanine (F). 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	Pathogenic	0.62
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Benign	0.10
Eigen_PC	Benign	-0.086
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Pathogenic	3.4	M
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.18
Sift	Uncertain	0.024	D
Sift4G	Benign	0.077	T
Polyphen		0.99	D
Vest4		0.22
MutPred		0.50		Loss of ubiquitination at K124 (P = 0.1296);
MVP		0.66
MPC		0.52
ClinPred		0.87	D
GERP RS		-0.50
Varity_R		0.27
gMVP		0.74

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: chr16-14766575;