chr7-103119955-T-C
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_Strong
The NM_001122838.3(NAPEPLD):c.563A>G(p.Tyr188Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,614,214 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
NAPEPLD
NM_001122838.3 missense
NM_001122838.3 missense
Scores
13
4
1
Clinical Significance
Conservation
PhyloP100: 6.22
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PM1
?
In a binding_site (size 0) in uniprot entity NAPEP_HUMAN
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.955
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NAPEPLD | NM_001122838.3 | c.563A>G | p.Tyr188Cys | missense_variant | 3/5 | ENST00000465647.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NAPEPLD | ENST00000465647.6 | c.563A>G | p.Tyr188Cys | missense_variant | 3/5 | 1 | NM_001122838.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152204Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461892Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727248
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152322Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74482
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 27, 2023 | The c.563A>G (p.Y188C) alteration is located in exon 3 (coding exon 2) of the NAPEPLD gene. This alteration results from a A to G substitution at nucleotide position 563, causing the tyrosine (Y) at amino acid position 188 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Pathogenic
D;D;D;D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H;H;H;H
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D;D
Sift4G
Pathogenic
D;D;D;D
Polyphen
D;D;D;D
Vest4
MutPred
Loss of phosphorylation at Y188 (P = 0.0666);Loss of phosphorylation at Y188 (P = 0.0666);Loss of phosphorylation at Y188 (P = 0.0666);Loss of phosphorylation at Y188 (P = 0.0666);
MVP
MPC
0.78
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.