rs373798047

Variant names:

• chr15-42142584-G-C
• rs373798047
• NM_213600.4:c.2273C>G

Your query was ambiguous. Multiple possible variants found:

• chr15-42142584-G-C
• chr15-42142584-G-A
• chr15-42142584-G-T

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.2273C>G​(p.Pro758Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000805 in 1,613,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: PLA2G4F NM_213600.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.21
• Publications: 2 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, 0.906

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.2273C>G	p.Pro758Arg	missense	Exon 19 of 20	NP_998765.3	Q68DD2-1
	PLA2G4F	NR_033151.2		n.2287C>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.2273C>G	p.Pro758Arg	missense	Exon 19 of 20	ENSP00000380442.4	Q68DD2-1
	PLA2G4F	ENST00000290497.11	TSL:1	n.*2017C>G		non_coding_transcript_exon	Exon 18 of 19	ENSP00000290497.7	H7BXJ8
	PLA2G4F	ENST00000562320.1	TSL:1	n.*78C>G		non_coding_transcript_exon	Exon 3 of 4	ENSP00000455037.1	H3BNW4

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152140 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251294 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000752 AC: 11 AN: 1461820 Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8 AN XY: 727218

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

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

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86242

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53400

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

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111990

Other (OTH) AF: 0.0000662 AC: 4 AN: 60394

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152140 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74336

African (AFR) AF: 0.0000241 AC: 1 AN: 41432

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	0.73
BayesDel_addAF	Pathogenic	0.44	D
BayesDel_noAF	Pathogenic	0.41
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	T
Eigen	Pathogenic	0.76
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.015	T
MetaRNN	Pathogenic	0.91	D
MetaSVM	Benign	-0.51	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		8.2
PrimateAI	Uncertain	0.54	T
REVEL	Uncertain	0.58
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.95
MVP		0.71
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.81
gMVP		0.82
Mutation Taster		=23/77	disease causing

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: rs373798047; hg19: chr15-42434782;