NM_213600.4:c.2218A>T

Variant names:

• chr15-42142639-T-A
• NM_213600.4:c.2218A>T

Variant summary

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

The NM_213600.4(PLA2G4F):​c.2218A>T​(p.Met740Leu) 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. 14/19 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. M740V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 30)
• Consequence: PLA2G4F NM_213600.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

Genes affected

PLA2G4F (HGNC:27396): (phospholipase A2 group IVF) Predicted to enable calcium ion binding activity; calcium-dependent phospholipase A2 activity; and calcium-dependent phospholipid binding activity. Predicted to be involved in glycerophospholipid catabolic process. Predicted to act upstream of or within several processes, including arachidonic acid secretion; cellular response to antibiotic; and prostaglandin biosynthetic process. Predicted to be located in cytoplasm. Predicted to be active in cytosol; ruffle membrane; and vesicle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0322282).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLA2G4F	NM_213600.4	c.2218A>T	p.Met740Leu	missense_variant	Exon 19 of 20	ENST00000397272.7	NP_998765.3
PLA2G4F	NR_033151.2	n.2232A>T		non_coding_transcript_exon_variant	Exon 18 of 19
PLA2G4F	XR_931785.1	n.2421A>T		non_coding_transcript_exon_variant	Exon 20 of 20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLA2G4F	ENST00000397272.7	c.2218A>T	p.Met740Leu	missense_variant	Exon 19 of 20	1	NM_213600.4	ENSP00000380442.4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 63

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.0080
DANN	Benign	0.64
DEOGEN2	Benign	0.0054	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.34	N
PrimateAI	Benign	0.25	T
REVEL	Benign	0.016
Sift4G	Benign	0.29	T
Polyphen		0.0	B
Vest4		0.10
MVP		0.14
ClinPred		0.033	T
GERP RS		-9.4
Varity_R		0.11
gMVP		0.31

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: chr15-42434837;