7-103115174-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001122838.3(NAPEPLD):c.942G>C(p.Arg314Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NAPEPLD NM_001122838.3 missense, splice_region
• Scores: Splicing: ADA: 0.9783
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.738

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAPEPLD	NM_001122838.3	c.942G>C	p.Arg314Ser	missense_variant, splice_region_variant	4/5	ENST00000465647.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAPEPLD	ENST00000465647.6	c.942G>C	p.Arg314Ser	missense_variant, splice_region_variant	4/5	1	NM_001122838.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2023

The c.942G>C (p.R314S) alteration is located in exon 4 (coding exon 3) of the NAPEPLD gene. This alteration results from a G to C substitution at nucleotide position 942, causing the arginine (R) at amino acid position 314 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
Cadd	Uncertain	26
Dann	Uncertain	0.99
DEOGEN2	Uncertain	0.53	D;D;D;D
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.94	D
MetaRNN	Uncertain	0.58	D;D;D;D
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.4	M;M;M;M
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-5.2	D;D;D;D
REVEL	Benign	0.27
Sift	Uncertain	0.0030	D;D;D;D
Sift4G	Uncertain	0.0090	D;D;D;D
Polyphen		0.99	D;D;D;D
Vest4		0.56
MutPred		0.54		Gain of ubiquitination at K318 (P = 0.0624);Gain of ubiquitination at K318 (P = 0.0624);Gain of ubiquitination at K318 (P = 0.0624);Gain of ubiquitination at K318 (P = 0.0624);
MVP		0.53
MPC		0.54
ClinPred		0.98	D
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.93
gMVP		0.90

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.98
dbscSNV1_RF	Pathogenic	0.89
SpliceAI score (max)		0.37		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.37		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-102755621;