chr19-48067815-T-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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. 13/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. T360I) has been classified as Uncertain significance.

• 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
• Publications: 24 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: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G4C	NM_003706.3	MANE Select	c.1078A>C	p.Thr360Pro	missense	Exon 13 of 17	NP_003697.2
	PLA2G4C	NM_001159322.2		c.1108A>C	p.Thr370Pro	missense	Exon 13 of 17	NP_001152794.1
	PLA2G4C	NM_001159323.2		c.1078A>C	p.Thr360Pro	missense	Exon 13 of 17	NP_001152795.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G4C	ENST00000599921.6	TSL:1 MANE Select	c.1078A>C	p.Thr360Pro	missense	Exon 13 of 17	ENSP00000469473.1
	PLA2G4C	ENST00000595161.5	TSL:3	c.142A>C	p.Thr48Pro	missense	Exon 2 of 5	ENSP00000469528.1
	PLA2G4C	ENST00000599111.5	TSL:2	c.1108A>C	p.Thr370Pro	missense	Exon 13 of 17	ENSP00000472546.1

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

GnomAD2 exomes AF: 0.0904 AC: 22743 AN: 251470 AF XY: 0.0893

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 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

African (AFR) AF: 0.232 AC: 7747 AN: 33386

American (AMR) AF: 0.0590 AC: 2638 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0842 AC: 2198 AN: 26106

East Asian (EAS) AF: 0.000706 AC: 28 AN: 39688

South Asian (SAS) AF: 0.0750 AC: 6465 AN: 86188

European-Finnish (FIN) AF: 0.105 AC: 5604 AN: 53404

Middle Eastern (MID) AF: 0.0924 AC: 532 AN: 5756

European-Non Finnish (NFE) AF: 0.0974 AC: 107995 AN: 1109168

Other (OTH) AF: 0.0921 AC: 5553 AN: 60292

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

African (AFR) AF: 0.229 AC: 9488 AN: 41420

American (AMR) AF: 0.0873 AC: 1334 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0824 AC: 286 AN: 3470

East Asian (EAS) AF: 0.000778 AC: 4 AN: 5144

South Asian (SAS) AF: 0.0731 AC: 353 AN: 4828

European-Finnish (FIN) AF: 0.110 AC: 1164 AN: 10574

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0983 AC: 6681 AN: 67960

Other (OTH) AF: 0.107 AC: 225 AN: 2110

Alfa AF: 0.104 Hom.: 2372

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 v4.9

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
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.52
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.38	T
MetaRNN	Benign	0.0049	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	2.0	M
PhyloP100		1.3
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.083
Sift	Benign	0.059	T
Sift4G	Uncertain	0.033	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
Mutation Taster		=98/2	polymorphism (auto)

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