15-42142638-A-C

Variant names:

• chr15-42142638-A-C
• rs918030428
• NM_213600.4:c.2219T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_213600.4(PLA2G4F):​c.2219T>G​(p.Met740Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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. M740K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PLA2G4F NM_213600.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.759
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.040502936).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_213600.4. 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
	PLA2G4F	NM_213600.4	MANE Select	c.2219T>G	p.Met740Arg	missense	Exon 19 of 20	NP_998765.3	Q68DD2-1
	PLA2G4F	NR_033151.2		n.2233T>G		non_coding_transcript_exon	Exon 18 of 19

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G4F	ENST00000397272.7	TSL:1 MANE Select	c.2219T>G	p.Met740Arg	missense	Exon 19 of 20	ENSP00000380442.4	Q68DD2-1
	PLA2G4F	ENST00000290497.11	TSL:1	n.*1963T>G		non_coding_transcript_exon	Exon 18 of 19	ENSP00000290497.7	H7BXJ8
	PLA2G4F	ENST00000562320.1	TSL:1	n.*24T>G		non_coding_transcript_exon	Exon 3 of 4	ENSP00000455037.1	H3BNW4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461842 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727230

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111978

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	14
DANN	Benign	0.69
DEOGEN2	Benign	0.00031	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-1.6	N
PhyloP100		0.76
PrimateAI	Benign	0.27	T
REVEL	Benign	0.081
Sift4G	Benign	0.57	T
Polyphen		0.0010	B
Vest4		0.17
MVP		0.36
ClinPred		0.035	T
GERP RS		3.6
Varity_R		0.17
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

dbSNP: rs918030428; hg19: chr15-42434836;