16-14688174-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_003561.3(PLA2G10):c.346G>A(p.Val116Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0041 (7 hom., cov: 16)
  • Exomes 𝑓: 0.0047 (5 hom.)
  • Failed GnomAD Quality Control
• Consequence: PLA2G10 NM_003561.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.39

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011835873).
• BP6: Variant 16-14688174-C-T is Benign according to our data. Variant chr16-14688174-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2457544.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLA2G10	NM_003561.3	c.346G>A	p.Val116Ile	missense_variant	3/4	ENST00000438167.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLA2G10	ENST00000438167.8	c.346G>A	p.Val116Ile	missense_variant	3/4	1	NM_003561.3	P1
PLA2G10	ENST00000567462.1	c.346G>A	p.Val116Ile	missense_variant, NMD_transcript_variant	3/5	3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 512 AN: 123714 Hom.: 7 Cov.: 16 FAILED QC

Gnomad AFR AF: 0.00119

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000435

Gnomad SAS AF: 0.000838

Gnomad FIN AF: 0.0106

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00651

Gnomad OTH AF: 0.00516

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00472 AC: 1763 AN: 373556 Hom.: 5 Cov.: 0 AF XY: 0.00459 AC XY: 906 AN XY: 197574

Gnomad4 AFR exome AF: 0.00119

Gnomad4 AMR exome AF: 0.00117

Gnomad4 ASJ exome AF: 0.0000950

Gnomad4 EAS exome AF: 0.000107

Gnomad4 SAS exome AF: 0.000688

Gnomad4 FIN exome AF: 0.00957

Gnomad4 NFE exome AF: 0.00648

Gnomad4 OTH exome AF: 0.00352

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00414 AC: 512 AN: 123792 Hom.: 7 Cov.: 16 AF XY: 0.00434 AC XY: 255 AN XY: 58772

Gnomad4 AFR AF: 0.00119

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000436

Gnomad4 SAS AF: 0.000841

Gnomad4 FIN AF: 0.0106

Gnomad4 NFE AF: 0.00651

Gnomad4 OTH AF: 0.00510

Alfa AF: 0.00834 Hom.: 2

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
Cadd	Benign	0.16
Dann	Benign	0.41
DEOGEN2	Benign	0.087	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0079	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.62	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.037
Sift	Benign	0.75	T
Sift4G	Benign	0.59	T
Polyphen		0.54	P
Vest4		0.073
MutPred		0.46		Gain of catalytic residue at V116 (P = 0.1583);
MVP		0.50
MPC		0.091
ClinPred		0.0058	T
GERP RS		-3.0
Varity_R		0.064
gMVP		0.45

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: rs1223454565; hg19: chr16-14782031;