chr7-103119619-G-C

Variant names:

• chr7-103119619-G-C
• rs748738700
• NM_001122838.3:c.899C>G

Variant summary

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

The NM_001122838.3(NAPEPLD):​c.899C>G​(p.Pro300Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P300T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NAPEPLD NM_001122838.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.76
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.898

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.899C>G	p.Pro300Arg	missense	Exon 3 of 5	NP_001116310.1	Q6IQ20
	NAPEPLD	NM_001386176.1		c.899C>G	p.Pro300Arg	missense	Exon 3 of 5	NP_001373105.1	Q6IQ20
	NAPEPLD	NM_001386177.1		c.899C>G	p.Pro300Arg	missense	Exon 3 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.899C>G	p.Pro300Arg	missense	Exon 3 of 5	ENSP00000419188.1	Q6IQ20
	NAPEPLD	ENST00000341533.8	TSL:1	c.899C>G	p.Pro300Arg	missense	Exon 3 of 6	ENSP00000340093.4	Q6IQ20
	NAPEPLD	ENST00000422589.5	TSL:1	n.899C>G		non_coding_transcript_exon	Exon 3 of 7	ENSP00000412376.1	Q6IQ20

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	Uncertain	0.42
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.59	D
Eigen	Pathogenic	0.99
Eigen_PC	Pathogenic	0.93
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Benign	0.032	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		9.8
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-7.2	D
REVEL	Uncertain	0.60
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.95
MutPred		0.63		Gain of catalytic residue at P300 (P = 0.0229)
MVP		0.69
MPC		0.72
ClinPred		1.0	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.86
gMVP		0.82
Mutation Taster		=13/87	disease causing

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: rs748738700; hg19: chr7-102760066;