chr19-48067831-C-G

Position:

• chr19-48067831-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003706.3(PLA2G4C):​c.1062G>C​(p.Lys354Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLA2G4C NM_003706.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.497

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1353277).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLA2G4C	NM_003706.3	c.1062G>C	p.Lys354Asn	missense_variant	13/17	ENST00000599921.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLA2G4C	ENST00000599921.6	c.1062G>C	p.Lys354Asn	missense_variant	13/17	1	NM_003706.3	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 06, 2022

The c.1062G>C (p.K354N) alteration is located in exon 13 (coding exon 12) of the PLA2G4C gene. This alteration results from a G to C substitution at nucleotide position 1062, causing the lysine (K) at amino acid position 354 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.1
DANN	Benign	0.89
DEOGEN2	Benign	0.0017	.;.;T;T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0046	N
LIST_S2	Benign	0.35	T;T;T;T;T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.14	T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.1	.;L;L;.;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.4	.;N;.;.;.
REVEL	Benign	0.038
Sift	Benign	0.42	.;T;.;.;.
Sift4G	Benign	0.46	T;T;T;.;.
Polyphen		0.020	.;.;B;.;.
Vest4		0.091
MutPred		0.49		.;Loss of methylation at K354 (P = 0.0063);Loss of methylation at K354 (P = 0.0063);.;.;
MVP		0.17
MPC		0.15
ClinPred		0.097	T
GERP RS		-3.6
Varity_R		0.055
gMVP		0.17

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-48571088;