chr19-48067875-T-C

Position:

• chr19-48067875-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_003706.3(PLA2G4C):​c.1018A>G​(p.Asn340Asp) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: PLA2G4C NM_003706.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0120

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054060668).
• BP6: Variant 19-48067875-T-C is Benign according to our data. Variant chr19-48067875-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3214095.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLA2G4C	NM_003706.3	c.1018A>G	p.Asn340Asp	missense_variant	13/17	ENST00000599921.6	NP_003697.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLA2G4C	ENST00000599921.6	c.1018A>G	p.Asn340Asp	missense_variant	13/17	1	NM_003706.3	ENSP00000469473.1
PLA2G4C	ENST00000595161.5	c.82A>G	p.Asn28Asp	missense_variant	2/5	3		ENSP00000469528.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 06, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.16
DANN	Benign	0.32
DEOGEN2	Benign	0.00049	.;.;T;T;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.00043	N
LIST_S2	Benign	0.35	T;T;T;T;T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.054	T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-1.1	.;N;N;.;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.46	.;N;.;.;.
REVEL	Benign	0.042
Sift	Benign	0.90	.;T;.;.;.
Sift4G	Benign	0.78	T;T;T;.;.
Polyphen		0.0	.;.;B;.;.
Vest4		0.028
MutPred		0.52		.;Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);.;.;
MVP		0.16
MPC		0.11
ClinPred		0.047	T
GERP RS		-0.72
Varity_R		0.045
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: chr19-48571132;