chr17-47592050-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_006310.4(NPEPPS):c.1355T>C(p.Ile452Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 29)
Exomes 𝑓: 0.0000032 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
NPEPPS
NM_006310.4 missense
NM_006310.4 missense
Scores
12
5
Clinical Significance
Conservation
PhyloP100: 6.09
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 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, NPEPPS
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NPEPPS | NM_006310.4 | c.1355T>C | p.Ile452Thr | missense_variant | 11/23 | ENST00000322157.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NPEPPS | ENST00000322157.9 | c.1355T>C | p.Ile452Thr | missense_variant | 11/23 | 1 | NM_006310.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 29
GnomAD3 genomes
?
Cov.:
29
GnomAD3 exomes AF: 0.0000127 AC: 3AN: 236950Hom.: 0 AF XY: 0.0000233 AC XY: 3AN XY: 128556
GnomAD3 exomes
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3
AN:
236950
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3
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128556
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000322 AC: 4AN: 1241876Hom.: 0 Cov.: 17 AF XY: 0.00000479 AC XY: 3AN XY: 626334
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
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4
AN:
1241876
Hom.:
Cov.:
17
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AC XY:
3
AN XY:
626334
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GnomAD4 genome ? Cov.: 29
GnomAD4 genome
?
Cov.:
29
Bravo
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ExAC
?
AF:
AC:
4
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 | Aug 12, 2021 | The c.1355T>C (p.I452T) alteration is located in exon 11 (coding exon 11) of the NPEPPS gene. This alteration results from a T to C substitution at nucleotide position 1355, causing the isoleucine (I) at amino acid position 452 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
B;B;.;.
Vest4
MutPred
0.75
.;Loss of stability (P = 0.0148);.;.;
MVP
MPC
2.3
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at