7-103103494-C-T

Variant names:

• chr7-103103494-C-T
• rs1170235381
• NM_001122838.3:c.1117G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001122838.3(NAPEPLD):​c.1117G>A​(p.Glu373Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign 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. E373Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NAPEPLD NM_001122838.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.11
• Publications: 0 publications found

Genes affected

NAPEPLD (HGNC:21683): (N-acyl phosphatidylethanolamine phospholipase D) NAPEPLD is a phospholipase D type enzyme that catalyzes the release of N-acylethanolamine (NAE) from N-acyl-phosphatidylethanolamine (NAPE) in the second step of the biosynthesis of N-acylethanolamine (Okamoto et al., 2004 [PubMed 14634025]).[supplied by OMIM, Oct 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2834611).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001122838.3. 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
	NAPEPLD	NM_001122838.3	MANE Select	c.1117G>A	p.Glu373Lys	missense	Exon 5 of 5	NP_001116310.1	Q6IQ20
	NAPEPLD	NM_001386176.1		c.1117G>A	p.Glu373Lys	missense	Exon 5 of 5	NP_001373105.1	Q6IQ20
	NAPEPLD	NM_001386177.1		c.1117G>A	p.Glu373Lys	missense	Exon 5 of 5	NP_001373106.1	Q6IQ20

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAPEPLD	ENST00000465647.6	TSL:1 MANE Select	c.1117G>A	p.Glu373Lys	missense	Exon 5 of 5	ENSP00000419188.1	Q6IQ20
	NAPEPLD	ENST00000341533.8	TSL:1	c.1117G>A	p.Glu373Lys	missense	Exon 5 of 6	ENSP00000340093.4	Q6IQ20
	NAPEPLD	ENST00000414118.2	TSL:1	n.342G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.046	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		4.1
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.098
Sift	Benign	0.25	T
Sift4G	Benign	0.53	T
Polyphen		0.073	B
Vest4		0.41
MutPred		0.51		Loss of stability (P = 0.0076)
MVP		0.45
MPC		0.20
ClinPred		0.81	D
GERP RS		5.9
Varity_R		0.37
gMVP		0.52
Mutation Taster		=66/34	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: rs1170235381; hg19: chr7-102743941;