chr15-41985883-C-A

Variant names:

• chr15-41985883-C-A
• rs1360243869
• NM_001395548.1:c.2071G>T

Variant summary

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

The NM_001395548.1(PLA2G4E):​c.2071G>T​(p.Asp691Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. D691N) 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: 5.43
• Publications: 4 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.892

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.2071G>T	p.Asp691Tyr	missense	Exon 18 of 20	NP_001382477.1	A0A8Q3WM91
	PLA2G4E	NM_001206670.1		c.2158G>T	p.Asp720Tyr	missense	Exon 18 of 20	NP_001193599.1	Q3MJ16-3
	PLA2G4E-AS1	NR_120334.1		n.543+4427C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G4E	ENST00000696112.1	MANE Select	c.2071G>T	p.Asp691Tyr	missense	Exon 18 of 20	ENSP00000512406.1	A0A8Q3WM91
	PLA2G4E	ENST00000547930.5	TSL:1	n.1447G>T		non_coding_transcript_exon	Exon 8 of 10
	PLA2G4E-AS1	ENST00000499478.2	TSL:1	n.543+4427C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	28
DANN	Uncertain	0.99
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.76
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.037	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Benign	-0.80	T
PhyloP100		5.4
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-8.8	D
REVEL	Uncertain	0.51
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Vest4		0.94
MVP		0.67
MPC		0.70
ClinPred		1.0	D
GERP RS		5.7
Varity_R		0.89
gMVP		0.93

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1360243869; hg19: chr15-42278081;