Genetic Variant PLA2G4C:p.Gly387Val (chr19-48062094-AC-TA) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is The variant received 2 classification points (ACMG Germline Pathogenicity v2019). PM2

The NM_003706.3(PLA2G4C):c.1160_1161delGTinsTA (p.Gly387Val) variant causes a missense change. Note: allele frequency estimates from gnomAD may be inaccurate for this variant type (MNP or indel longer than 3 bp) due to technology limitations. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Other variants at the same amino acid position have been reported in ClinVar (not pathogenic): p.G387A: Uncertain_significance (ClinVar VariationId 2376460, 1 star); p.G387S: Uncertain_significance (ClinVar VariationId 4138261, 1 star)

Frequency

Genomes: not found (cov: 32)

Consequence

PLA2G4C
NM_003706.3 missense

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.59

Publications

0 publications found

Variant links:

Genes affected

PLA2G4C (HGNC:9037): (phospholipase A2 group IVC) This gene encodes a protein which is a member of the phospholipase A2 enzyme family which hydrolyzes glycerophospholipids to produce free fatty acids and lysophospholipids, both of which serve as precursors in the production of signaling molecules. The encoded protein has been shown to be a calcium-independent and membrane bound enzyme. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2009]

PLA2G4C links:

PLA2G4C-AS1 (HGNC:51585): ()

PLA2G4C-AS1 links:

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new If you want to explore the variant's impact on the transcript NM_003706.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 2 points.

Show applied only (1)

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Absent from gnomAD (AR/unknown gene) — PM2; Absent from gnomAD at well-covered site (MOI: unknown) (threshold 0.001) — PM2 moderate.

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_003706.3. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
PLA2G4C NM_003706.3	MANE Select	c.1160_1161delGTinsTA p.Gly387Val	missense	N/A	Prot: NP_003697.2 UniProt: Q9UP65-1
PLA2G4C NM_001159322.2		c.1190_1191delGTinsTA p.Gly397Val	missense	N/A	Prot: NP_001152794.1 UniProt: Q9UP65-3
PLA2G4C NM_001159323.2		c.1160_1161delGTinsTA p.Gly387Val	missense	N/A	Prot: NP_001152795.1 UniProt: Q9UP65-2

PLA2G4C NM_003706.3

MANE Select

HGVSc / HGVSpc.1160_1161delGTinsTAp.Gly387Val

Exon rankN/A

missense

Prot: NP_003697.2UniProt: Q9UP65-1

PLA2G4C NM_001159322.2

HGVSc / HGVSpc.1190_1191delGTinsTAp.Gly397Val

Exon rankN/A

missense

Prot: NP_001152794.1UniProt: Q9UP65-3

PLA2G4C NM_001159323.2

HGVSc / HGVSpc.1160_1161delGTinsTAp.Gly387Val

Exon rankN/A

missense

Prot: NP_001152795.1UniProt: Q9UP65-2

Ensembl Transcripts

Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
PLA2G4C ENST00000599921.6	TSL:1MANE Select	c.1160_1161delGTinsTA p.Gly387Val	missense	N/A	Prot: ENSP00000469473.1 UniProt: Q9UP65-1
PLA2G4C ENST00000595161.5	TSL:3	c.224_225delGTinsTA p.Gly75Val	missense	N/A	Prot: ENSP00000469528.1 UniProt: M0QY18
PLA2G4C ENST00000887096.1		c.1217_1218delGTinsTA p.Gly406Val	missense	N/A	Prot: ENSP00000557155.1 UniProt: A0ACI8QRI2

PLA2G4C ENST00000599921.6

TSL:1MANE Select

HGVSc / HGVSpc.1160_1161delGTinsTAp.Gly387Val

Exon rankN/A

missense

Prot: ENSP00000469473.1UniProt: Q9UP65-1

PLA2G4C ENST00000595161.5

TSL:3

HGVSc / HGVSpc.224_225delGTinsTAp.Gly75Val

Exon rankN/A

missense

Prot: ENSP00000469528.1UniProt: M0QY18

PLA2G4C ENST00000887096.1

HGVSc / HGVSpc.1217_1218delGTinsTAp.Gly406Val

Exon rankN/A

missense

Prot: ENSP00000557155.1UniProt: A0ACI8QRI2

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 2 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:32
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:32

Showing 2 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
PhyloP100	Benign	1.6

Showing 1 of 1 scores

Splicing Scores

No splicing scores have been computed for this variant.

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational Scores

Splicing Scores

MaveDB functional evidence ?

Publications

Other links and lift over

MaveDB functional evidence