chr19-48067875-T-C

Variant names:

• chr19-48067875-T-C
• NM_003706.3:c.1018A>G

Variant summary

Our verdict is Likely benign. The variant received -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. 16/22 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
• Publications: 0 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: Likely_benign. The variant received -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 VariationId is 3214095.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G4C	NM_003706.3	MANE Select	c.1018A>G	p.Asn340Asp	missense	Exon 13 of 17	NP_003697.2	Q9UP65-1
	PLA2G4C	NM_001159322.2		c.1048A>G	p.Asn350Asp	missense	Exon 13 of 17	NP_001152794.1	Q9UP65-3
	PLA2G4C	NM_001159323.2		c.1018A>G	p.Asn340Asp	missense	Exon 13 of 17	NP_001152795.1	Q9UP65-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G4C	ENST00000599921.6	TSL:1 MANE Select	c.1018A>G	p.Asn340Asp	missense	Exon 13 of 17	ENSP00000469473.1	Q9UP65-1
	PLA2G4C	ENST00000595161.5	TSL:3	c.82A>G	p.Asn28Asp	missense	Exon 2 of 5	ENSP00000469528.1	M0QY18
	PLA2G4C	ENST00000887096.1		c.1075A>G	p.Asn359Asp	missense	Exon 14 of 18	ENSP00000557155.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.00043	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-1.1	N
PhyloP100		0.012
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.46	N
REVEL	Benign	0.042
Sift	Benign	0.90	T
Sift4G	Benign	0.78	T
Polyphen		0.0	B
Vest4		0.028
MutPred		0.52		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
Mutation Taster		=99/1	polymorphism

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

hg19: chr19-48571132;