rs201127134

Variant names:

• chr19-48062095-C-G
• rs201127134
• NM_003706.3:c.1160G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-48062095-C-G
• chr19-48062095-C-A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_003706.3(PLA2G4C):​c.1160G>C​(p.Gly387Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000348 in 1,611,200 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G387S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000035 (1 hom.)
• Consequence: PLA2G4C NM_003706.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.59
• Publications: 1 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]

PLA2G4C-AS1 (HGNC:51585): (PLA2G4C antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3155694).

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.1160G>C	p.Gly387Ala	missense	Exon 14 of 17	NP_003697.2	Q9UP65-1
	PLA2G4C	NM_001159322.2		c.1190G>C	p.Gly397Ala	missense	Exon 14 of 17	NP_001152794.1	Q9UP65-3
	PLA2G4C	NM_001159323.2		c.1160G>C	p.Gly387Ala	missense	Exon 14 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.1160G>C	p.Gly387Ala	missense	Exon 14 of 17	ENSP00000469473.1	Q9UP65-1
	PLA2G4C	ENST00000595161.5	TSL:3	c.224G>C	p.Gly75Ala	missense	Exon 3 of 5	ENSP00000469528.1	M0QY18
	PLA2G4C	ENST00000887096.1		c.1217G>C	p.Gly406Ala	missense	Exon 15 of 18	ENSP00000557155.1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152162 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000525 AC: 13 AN: 247794 AF XY: 0.0000598

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000175

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000536

Gnomad OTH exome AF: 0.000167

GnomAD4 exome AF: 0.0000350 AC: 51 AN: 1459038 Hom.: 1 Cov.: 31 AF XY: 0.0000482 AC XY: 35 AN XY: 725618

African (AFR) AF: 0.00 AC: 0 AN: 33360

American (AMR) AF: 0.000225 AC: 10 AN: 44470

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25968

East Asian (EAS) AF: 0.00 AC: 0 AN: 39478

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 85884

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53332

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5754

European-Non Finnish (NFE) AF: 0.0000324 AC: 36 AN: 1110528

Other (OTH) AF: 0.0000498 AC: 3 AN: 60264

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152162 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74318

African (AFR) AF: 0.00 AC: 0 AN: 41424

American (AMR) AF: 0.00 AC: 0 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68048

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.0000565 Hom.: 0

Bravo AF: 0.0000831

ExAC AF: 0.0000494 AC: 6

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	Pathogenic	0.68
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.13	T
Eigen	Benign	0.026
Eigen_PC	Benign	-0.089
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		1.6
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.18
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.034	D
Polyphen		1.0	D
Vest4		0.43
MVP		0.37
MPC		0.50
ClinPred		0.42	T
GERP RS		1.6
Varity_R		0.48
gMVP		0.70
Mutation Taster		=85/15	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: rs201127134; hg19: chr19-48565352;