7-103119674-C-A

Variant names:

• chr7-103119674-C-A
• rs532713419
• NM_001122838.3:c.844G>T

Variant summary

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

The NM_001122838.3(NAPEPLD):​c.844G>T​(p.Ala282Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,613,946 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict 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. A282T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: NAPEPLD NM_001122838.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.98
• 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=0.30522972).

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.844G>T	p.Ala282Ser	missense	Exon 3 of 5	NP_001116310.1	Q6IQ20
	NAPEPLD	NM_001386176.1		c.844G>T	p.Ala282Ser	missense	Exon 3 of 5	NP_001373105.1	Q6IQ20
	NAPEPLD	NM_001386177.1		c.844G>T	p.Ala282Ser	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.844G>T	p.Ala282Ser	missense	Exon 3 of 5	ENSP00000419188.1	Q6IQ20
	NAPEPLD	ENST00000341533.8	TSL:1	c.844G>T	p.Ala282Ser	missense	Exon 3 of 6	ENSP00000340093.4	Q6IQ20
	NAPEPLD	ENST00000422589.5	TSL:1	n.844G>T		non_coding_transcript_exon	Exon 3 of 7	ENSP00000412376.1	Q6IQ20

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151966 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251250 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461862 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727236

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

American (AMR) AF: 0.00 AC: 0 AN: 44724

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

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

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112008

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

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152084 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74340

African (AFR) AF: 0.00 AC: 0 AN: 41478

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67988

Other (OTH) AF: 0.00 AC: 0 AN: 2106

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.090
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.0082
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	1.5	L
PhyloP100		4.0
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.25
Sift	Benign	0.28	T
Sift4G	Benign	0.36	T
Polyphen		0.21	B
Vest4		0.31
MutPred		0.63		Gain of glycosylation at A282 (P = 0.007)
MVP		0.74
MPC		0.18
ClinPred		0.62	D
GERP RS		5.1
Varity_R		0.49
gMVP		0.78
Mutation Taster		=51/49	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: rs532713419; hg19: chr7-102760121;