chr19-48067815-T-G

Variant names:

• chr19-48067815-T-G
• rs11564620
• NM_003706.3:c.1078A>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003706.3(PLA2G4C):​c.1078A>C​(p.Thr360Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0983 in 1,610,696 control chromosomes in the GnomAD database, including 9,094 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.13 (1579 hom., cov: 31)
  • Exomes 𝑓: 0.095 (7515 hom.)
• Consequence: PLA2G4C NM_003706.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004939705).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G4C	NM_003706.3	c.1078A>C	p.Thr360Pro	missense_variant	Exon 13 of 17	ENST00000599921.6	NP_003697.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G4C	ENST00000599921.6	c.1078A>C	p.Thr360Pro	missense_variant	Exon 13 of 17	1	NM_003706.3	ENSP00000469473.1
PLA2G4C	ENST00000595161.5	c.142A>C	p.Thr48Pro	missense_variant	Exon 2 of 5	3		ENSP00000469528.1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19636 AN: 151874 Hom.: 1579 Cov.: 31

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.0876

Gnomad ASJ AF: 0.0824

Gnomad EAS AF: 0.000776

Gnomad SAS AF: 0.0728

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0983

Gnomad OTH AF: 0.108

GnomAD3 exomes AF: 0.0904 AC: 22743 AN: 251470 Hom.: 1354 AF XY: 0.0893 AC XY: 12130 AN XY: 135902

Gnomad AFR exome AF: 0.232

Gnomad AMR exome AF: 0.0555

Gnomad ASJ exome AF: 0.0846

Gnomad EAS exome AF: 0.000815

Gnomad SAS exome AF: 0.0734

Gnomad FIN exome AF: 0.104

Gnomad NFE exome AF: 0.0983

Gnomad OTH exome AF: 0.0830

GnomAD4 exome AF: 0.0951 AC: 138760 AN: 1458704 Hom.: 7515 Cov.: 29 AF XY: 0.0948 AC XY: 68832 AN XY: 725838

Gnomad4 AFR exome AF: 0.232

Gnomad4 AMR exome AF: 0.0590

Gnomad4 ASJ exome AF: 0.0842

Gnomad4 EAS exome AF: 0.000706

Gnomad4 SAS exome AF: 0.0750

Gnomad4 FIN exome AF: 0.105

Gnomad4 NFE exome AF: 0.0974

Gnomad4 OTH exome AF: 0.0921

GnomAD4 genome AF: 0.129 AC: 19647 AN: 151992 Hom.: 1579 Cov.: 31 AF XY: 0.128 AC XY: 9510 AN XY: 74310

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.0873

Gnomad4 ASJ AF: 0.0824

Gnomad4 EAS AF: 0.000778

Gnomad4 SAS AF: 0.0731

Gnomad4 FIN AF: 0.110

Gnomad4 NFE AF: 0.0983

Gnomad4 OTH AF: 0.107

Alfa AF: 0.102 Hom.: 1604

Bravo AF: 0.132

TwinsUK AF: 0.0887 AC: 329

ALSPAC AF: 0.0960 AC: 370

ESP6500AA AF: 0.223 AC: 983

ESP6500EA AF: 0.100 AC: 862

ExAC AF: 0.0940 AC: 11416

Asia WGS AF: 0.0500 AC: 176 AN: 3478

EpiCase AF: 0.0994

EpiControl AF: 0.0984

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	16
DANN	Benign	0.80
DEOGEN2	Benign	0.018	.;.;T;T;.
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.38	T;T;T;T;T
MetaRNN	Benign	0.0049	T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	2.0	.;M;M;.;.
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.1	.;D;.;.;.
REVEL	Benign	0.083
Sift	Benign	0.059	.;T;.;.;.
Sift4G	Uncertain	0.033	D;D;D;.;.
Polyphen		0.77	.;.;P;.;.
Vest4		0.073
MPC		0.55
ClinPred		0.044	T
GERP RS		1.7
Varity_R		0.28
gMVP		0.50

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: rs11564620; hg19: chr19-48571072; COSMIC: COSV62786119; COSMIC: COSV62786119;