19-48062024-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_003706.3(PLA2G4C):c.1231G>A(p.Asp411Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000813 in 1,613,742 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0041 (5 hom., cov: 32)
  • Exomes 𝑓: 0.00047 (8 hom.)
• Consequence: PLA2G4C NM_003706.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.94

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

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010666877).
• BP6: Variant 19-48062024-C-T is Benign according to our data. Variant chr19-48062024-C-T is described in ClinVar as [Benign]. Clinvar id is 723608.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLA2G4C	NM_003706.3	c.1231G>A	p.Asp411Asn	missense_variant	14/17	ENST00000599921.6
PLA2G4C-AS1	NR_132363.1	n.320C>T		non_coding_transcript_exon_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLA2G4C	ENST00000599921.6	c.1231G>A	p.Asp411Asn	missense_variant	14/17	1	NM_003706.3	A2
PLA2G4C-AS1	ENST00000596552.1	n.263C>T		non_coding_transcript_exon_variant	3/5	3

Frequencies

GnomAD3 genomes AF: 0.00412 AC: 627 AN: 152024 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.0142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00125

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00106 AC: 266 AN: 251172 Hom.: 2 AF XY: 0.000751 AC XY: 102 AN XY: 135754

Gnomad AFR exome AF: 0.0131

Gnomad AMR exome AF: 0.000810

Gnomad ASJ exome AF: 0.00119

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000968

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000468 AC: 684 AN: 1461600 Hom.: 8 Cov.: 31 AF XY: 0.000396 AC XY: 288 AN XY: 727098

Gnomad4 AFR exome AF: 0.0159

Gnomad4 AMR exome AF: 0.000760

Gnomad4 ASJ exome AF: 0.00142

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000279

Gnomad4 OTH exome AF: 0.000812

GnomAD4 genome AF: 0.00413 AC: 628 AN: 152142 Hom.: 5 Cov.: 32 AF XY: 0.00378 AC XY: 281 AN XY: 74360

Gnomad4 AFR AF: 0.0142

Gnomad4 AMR AF: 0.00124

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00184 Hom.: 0

Bravo AF: 0.00476

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0125 AC: 55

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.00123 AC: 150

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.57
Cadd	Benign	18
Dann	Uncertain	1.0
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.78	T;T;T;T
MetaRNN	Benign	0.011	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	0.99	N;N
PrimateAI	Uncertain	0.56	T
Sift4G	Benign	0.12	T;T;T;.
Polyphen		0.70	.;.;P;.
Vest4		0.60
MVP		0.54
MPC		0.31
ClinPred		0.086	T
GERP RS		2.8
Varity_R		0.38
gMVP		0.47

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: rs11564638; hg19: chr19-48565281; COSMIC: COSV62785347; COSMIC: COSV62785347;