17-47582823-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4
The NM_006310.4(NPEPPS):c.622A>G(p.Lys208Glu) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000018 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
NPEPPS
NM_006310.4 missense
NM_006310.4 missense
Scores
1
4
12
Clinical Significance
Conservation
PhyloP100: 7.22
Genes affected
NPEPPS (HGNC:7900): (aminopeptidase puromycin sensitive) This gene encodes the puromycin-sensitive aminopeptidase, a zinc metallopeptidase which hydrolyzes amino acids from the N-terminus of its substrate. The protein has been localized to both the cytoplasm and to cellular membranes. This enzyme degrades enkaphalins in the brain, and studies in mouse suggest that it is involved in proteolytic events regulating the cell cycle. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, NPEPPS
BP4
?
Computational evidence support a benign effect (MetaRNN=0.28000575).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NPEPPS | NM_006310.4 | c.622A>G | p.Lys208Glu | missense_variant | 5/23 | ENST00000322157.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NPEPPS | ENST00000322157.9 | c.622A>G | p.Lys208Glu | missense_variant | 5/23 | 1 | NM_006310.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 2AN: 151944Hom.: 0 Cov.: 31 FAILED QC
GnomAD3 genomes
?
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2
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31
FAILED QC
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GnomAD3 exomes AF: 0.00000863 AC: 1AN: 115814Hom.: 0 AF XY: 0.0000163 AC XY: 1AN XY: 61444
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000183 AC: 13AN: 710720Hom.: 0 Cov.: 9 AF XY: 0.0000265 AC XY: 10AN XY: 377504
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GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.0000132 AC: 2AN: 151944Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74244
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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 13, 2023 | The c.622A>G (p.K208E) alteration is located in exon 5 (coding exon 5) of the NPEPPS gene. This alteration results from a A to G substitution at nucleotide position 622, causing the lysine (K) at amino acid position 208 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
0.24
.;B;B
Vest4
0.57, 0.58
MutPred
0.54
.;.;Loss of ubiquitination at K208 (P = 0.0381);
MVP
MPC
2.8
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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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