19-48053118-C-T

Variant names:

• chr19-48053118-C-T
• rs781443003
• NM_003706.3:c.1459G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003706.3(PLA2G4C):​c.1459G>A​(p.Asp487Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,455,098 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: PLA2G4C NM_003706.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.614
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.097449094).

Variant Effect in Transcripts

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

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G4C	NM_003706.3	MANE Select	c.1459G>A	p.Asp487Asn	missense	Exon 16 of 17	NP_003697.2	Q9UP65-1
	PLA2G4C	NM_001159322.2		c.1489G>A	p.Asp497Asn	missense	Exon 16 of 17	NP_001152794.1	Q9UP65-3
	PLA2G4C	NM_001159323.2		c.1459G>A	p.Asp487Asn	missense	Exon 16 of 17	NP_001152795.1	Q9UP65-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G4C	ENST00000599921.6	TSL:1 MANE Select	c.1459G>A	p.Asp487Asn	missense	Exon 16 of 17	ENSP00000469473.1	Q9UP65-1
	PLA2G4C	ENST00000594790.1	TSL:1	n.212G>A		non_coding_transcript_exon	Exon 2 of 3
	PLA2G4C	ENST00000887096.1		c.1516G>A	p.Asp506Asn	missense	Exon 17 of 18	ENSP00000557155.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000120 AC: 3 AN: 250532 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000140

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000124 AC: 18 AN: 1455098 Hom.: 0 Cov.: 30 AF XY: 0.0000138 AC XY: 10 AN XY: 722444

African (AFR) AF: 0.00 AC: 0 AN: 33396

American (AMR) AF: 0.00 AC: 0 AN: 44578

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26070

East Asian (EAS) AF: 0.0000507 AC: 2 AN: 39472

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 85916

European-Finnish (FIN) AF: 0.0000752 AC: 4 AN: 53190

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00000723 AC: 8 AN: 1106580

Other (OTH) AF: 0.0000333 AC: 2 AN: 60148

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.00000824 AC: 1

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.8
DANN	Benign	0.67
DEOGEN2	Benign	0.00047	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0011	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.5	L
PhyloP100		-0.61
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.52	N
REVEL	Benign	0.071
Sift	Benign	0.48	T
Sift4G	Benign	0.73	T
Polyphen		0.91	P
Vest4		0.089
MutPred		0.61		Loss of ubiquitination at K490 (P = 0.077)
MVP		0.26
MPC		0.18
ClinPred		0.43	T
GERP RS		-4.8
Varity_R		0.029
gMVP		0.18
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs781443003; hg19: chr19-48556375;