NM_213600.4:c.2288T>C

Variant names:

• chr15-42142569-A-G
• rs2048836235
• NM_213600.4:c.2288T>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_213600.4(PLA2G4F):​c.2288T>C​(p.Phe763Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PLA2G4F NM_213600.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.67
• 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.883

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.2288T>C	p.Phe763Ser	missense	Exon 19 of 20	NP_998765.3	Q68DD2-1
	PLA2G4F	NR_033151.2		n.2302T>C		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.2288T>C	p.Phe763Ser	missense	Exon 19 of 20	ENSP00000380442.4	Q68DD2-1
	PLA2G4F	ENST00000290497.11	TSL:1	n.*2032T>C		non_coding_transcript_exon	Exon 18 of 19	ENSP00000290497.7	H7BXJ8
	PLA2G4F	ENST00000562320.1	TSL:1	n.*93T>C		non_coding_transcript_exon	Exon 3 of 4	ENSP00000455037.1	H3BNW4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.44	D
BayesDel_noAF	Pathogenic	0.39
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.011	T
MetaRNN	Pathogenic	0.88	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		7.7
PrimateAI	Uncertain	0.71	T
REVEL	Uncertain	0.58
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.95
MVP		0.64
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.90
gMVP		0.83

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

dbSNP: rs2048836235; hg19: chr15-42434767;