NM_001395548.1:c.2224C>G

Variant names:

• chr15-41984511-G-C
• rs1371996626
• NM_001395548.1:c.2224C>G

Variant summary

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

The NM_001395548.1(PLA2G4E):​c.2224C>G​(p.Pro742Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PLA2G4E NM_001395548.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.33
• Publications: 0 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: 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=0.06798002).

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.2224C>G	p.Pro742Ala	missense	Exon 19 of 20	NP_001382477.1	A0A8Q3WM91
	PLA2G4E	NM_001206670.1		c.2311C>G	p.Pro771Ala	missense	Exon 19 of 20	NP_001193599.1	Q3MJ16-3
	PLA2G4E-AS1	NR_120334.1		n.543+3055G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLA2G4E	ENST00000696112.1	MANE Select	c.2224C>G	p.Pro742Ala	missense	Exon 19 of 20	ENSP00000512406.1	A0A8Q3WM91
	PLA2G4E	ENST00000547930.5	TSL:1	n.1600C>G		non_coding_transcript_exon	Exon 9 of 10
	PLA2G4E-AS1	ENST00000499478.2	TSL:1	n.543+3055G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 249004 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461666 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727122

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

American (AMR) AF: 0.0000447 AC: 2 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

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

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111834

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 32

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	Benign	0.063
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.080
DANN	Benign	0.78
DEOGEN2	Benign	0.19	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-0.90	T
PhyloP100		-1.3
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.94	N
REVEL	Benign	0.013
Sift	Benign	0.25	T
Sift4G	Benign	0.65	T
Vest4		0.22
MVP		0.092
MPC		0.14
ClinPred		0.028	T
GERP RS		-4.5
Varity_R		0.034
gMVP		0.30
Mutation Taster		=98/2	polymorphism

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: rs1371996626; hg19: chr15-42276709;