15-41987366-G-C

Variant names:

• chr15-41987366-G-C
• rs745626061
• NM_001395548.1:c.1754C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001395548.1(PLA2G4E):​c.1754C>G​(p.Pro585Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. P585L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PLA2G4E NM_001395548.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.17
• Publications: 2 publications found

Genes affected

PLA2G4E (HGNC:24791): (phospholipase A2 group IVE) This gene encodes a member of the cytosolic phospholipase A2 group IV family. Members of this family are involved in regulation of membrane tubule-mediated transport. The enzyme encoded by this member of the family plays a role in trafficking through the clathrin-independent endocytic pathway. The enzyme regulates the recycling process via formation of tubules that transport internalized clathrin-independent cargo proteins back to the cell surface. [provided by RefSeq, Jan 2017]

PLA2G4E-AS1 (HGNC:51419): (PLA2G4E antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395548.1. 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
	PLA2G4E	NM_001395548.1	MANE Select	c.1754C>G	p.Pro585Arg	missense	Exon 17 of 20	NP_001382477.1	A0A8Q3WM91
	PLA2G4E	NM_001206670.1		c.1841C>G	p.Pro614Arg	missense	Exon 17 of 20	NP_001193599.1	Q3MJ16-3
	PLA2G4E-AS1	NR_120334.1		n.543+5910G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G4E	ENST00000696112.1	MANE Select	c.1754C>G	p.Pro585Arg	missense	Exon 17 of 20	ENSP00000512406.1	A0A8Q3WM91
	PLA2G4E	ENST00000547930.5	TSL:1	n.1130C>G		non_coding_transcript_exon	Exon 7 of 10
	PLA2G4E-AS1	ENST00000499478.2	TSL:1	n.543+5910G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.042	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Uncertain	1.0
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-1.2	T
PhyloP100		6.2
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Benign	0.21
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.012	D
Vest4		0.52
MVP		0.58
MPC		0.65
ClinPred		0.99	D
GERP RS		5.8
Varity_R		0.57
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs745626061; hg19: chr15-42279564;