7-103119754-C-T

Variant names:

• chr7-103119754-C-T
• rs1330738341
• NM_001122838.3:c.764G>A

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001122838.3(NAPEPLD):​c.764G>A​(p.Cys255Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. C255F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NAPEPLD NM_001122838.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.93
• 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.951

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.764G>A	p.Cys255Tyr	missense	Exon 3 of 5	NP_001116310.1	Q6IQ20
	NAPEPLD	NM_001386176.1		c.764G>A	p.Cys255Tyr	missense	Exon 3 of 5	NP_001373105.1	Q6IQ20
	NAPEPLD	NM_001386177.1		c.764G>A	p.Cys255Tyr	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.764G>A	p.Cys255Tyr	missense	Exon 3 of 5	ENSP00000419188.1	Q6IQ20
	NAPEPLD	ENST00000341533.8	TSL:1	c.764G>A	p.Cys255Tyr	missense	Exon 3 of 6	ENSP00000340093.4	Q6IQ20
	NAPEPLD	ENST00000422589.5	TSL:1	n.764G>A		non_coding_transcript_exon	Exon 3 of 7	ENSP00000412376.1	Q6IQ20

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461876 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727238

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44714

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

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

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.58	D
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.95	D
MetaSVM	Uncertain	0.26	D
MutationAssessor	Uncertain	2.6	M
PhyloP100		5.9
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Pathogenic	0.73
Sift	Uncertain	0.016	D
Sift4G	Benign	0.099	T
Polyphen		0.59	P
Vest4		0.74
MutPred		0.86		Loss of methylation at K256 (P = 0.0127)
MVP		0.83
MPC		0.85
ClinPred		1.0	D
GERP RS		4.8
Varity_R		0.94
gMVP		0.90
Mutation Taster		=27/73	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: rs1330738341; hg19: chr7-102760201; COSMIC: COSV100439848; COSMIC: COSV100439848;