rs771908409

Variant names:

• chr19-48067839-C-T
• rs771908409
• NM_003706.3:c.1054G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_003706.3(PLA2G4C):​c.1054G>A​(p.Ala352Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000297 in 1,613,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: PLA2G4C NM_003706.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.26
• 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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.043954372).

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.1054G>A	p.Ala352Thr	missense	Exon 13 of 17	NP_003697.2	Q9UP65-1
	PLA2G4C	NM_001159322.2		c.1084G>A	p.Ala362Thr	missense	Exon 13 of 17	NP_001152794.1	Q9UP65-3
	PLA2G4C	NM_001159323.2		c.1054G>A	p.Ala352Thr	missense	Exon 13 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.1054G>A	p.Ala352Thr	missense	Exon 13 of 17	ENSP00000469473.1	Q9UP65-1
	PLA2G4C	ENST00000595161.5	TSL:3	c.118G>A	p.Ala40Thr	missense	Exon 2 of 5	ENSP00000469528.1	M0QY18
	PLA2G4C	ENST00000887096.1		c.1111G>A	p.Ala371Thr	missense	Exon 14 of 18	ENSP00000557155.1

Frequencies

GnomAD3 genomes AF: 0.000131 AC: 20 AN: 152146 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000437 AC: 11 AN: 251486 AF XY: 0.0000441

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000192 AC: 28 AN: 1461510 Hom.: 0 Cov.: 30 AF XY: 0.0000220 AC XY: 16 AN XY: 727064

African (AFR) AF: 0.000478 AC: 16 AN: 33470

American (AMR) AF: 0.0000447 AC: 2 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39696

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111684

Other (OTH) AF: 0.0000497 AC: 3 AN: 60382

GnomAD4 genome AF: 0.000131 AC: 20 AN: 152146 Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13 AN XY: 74308

African (AFR) AF: 0.000410 AC: 17 AN: 41442

American (AMR) AF: 0.00 AC: 0 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68032

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.0000709 Hom.: 0

Bravo AF: 0.000132

ExAC AF: 0.0000247 AC: 3

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	0.14
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.5
DANN	Benign	0.74
DEOGEN2	Benign	0.00054	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0011	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.69	N
PhyloP100		-1.3
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.31	N
REVEL	Benign	0.0060
Sift	Benign	0.18	T
Sift4G	Benign	0.092	T
Polyphen		0.063	B
Vest4		0.060
MVP		0.18
MPC		0.11
ClinPred		0.0080	T
GERP RS		-5.6
Varity_R		0.026
gMVP		0.12
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs771908409; hg19: chr19-48571096; COSMIC: COSV100843882; COSMIC: COSV100843882;