chr17-47590876-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP2
The NM_006310.4(NPEPPS):c.1255A>G(p.Ile419Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000511 in 1,566,422 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000042 ( 0 hom. )
Consequence
NPEPPS
NM_006310.4 missense
NM_006310.4 missense
Scores
4
4
9
Clinical Significance
Conservation
PhyloP100: 9.16
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 1 ACMG points.
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.1255A>G | p.Ile419Val | missense_variant | 10/23 | ENST00000322157.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NPEPPS | ENST00000322157.9 | c.1255A>G | p.Ile419Val | missense_variant | 10/23 | 1 | NM_006310.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152114Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000424 AC: 6AN: 1414308Hom.: 0 Cov.: 30 AF XY: 0.00000429 AC XY: 3AN XY: 698496
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152114Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74328
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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.1255A>G (p.I419V) alteration is located in exon 10 (coding exon 10) of the NPEPPS gene. This alteration results from a A to G substitution at nucleotide position 1255, causing the isoleucine (I) at amino acid position 419 to be replaced by a valine (V). 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
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Pathogenic
D;D;T;T
Sift4G
Benign
T;T;T;T
Polyphen
D;D;.;.
Vest4
MutPred
0.74
.;Gain of disorder (P = 0.0978);.;.;
MVP
MPC
2.5
ClinPred
D
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