chr17-47585524-C-T
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_StrongBS2
The NM_006310.4(NPEPPS):c.673C>T(p.Pro225Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000223 in 1,612,636 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000023 ( 0 hom. )
Consequence
NPEPPS
NM_006310.4 missense
NM_006310.4 missense
Scores
1
2
14
Clinical Significance
Conservation
PhyloP100: 3.91
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 Benign. Variant got -7 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, NPEPPS
BP4
?
Computational evidence support a benign effect (MetaRNN=0.03860089).
BS2
?
High AC in GnomAdExome at 30 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NPEPPS | NM_006310.4 | c.673C>T | p.Pro225Ser | missense_variant | 6/23 | ENST00000322157.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NPEPPS | ENST00000322157.9 | c.673C>T | p.Pro225Ser | missense_variant | 6/23 | 1 | NM_006310.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000198 AC: 3AN: 151682Hom.: 0 Cov.: 31
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000120 AC: 30AN: 249192Hom.: 0 AF XY: 0.000111 AC XY: 15AN XY: 135186
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GnomAD4 exome AF: 0.0000226 AC: 33AN: 1460954Hom.: 0 Cov.: 30 AF XY: 0.0000220 AC XY: 16AN XY: 726790
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GnomAD4 genome ? AF: 0.0000198 AC: 3AN: 151682Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74066
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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 | Oct 06, 2021 | The c.673C>T (p.P225S) alteration is located in exon 6 (coding exon 6) of the NPEPPS gene. This alteration results from a C to T substitution at nucleotide position 673, causing the proline (P) at amino acid position 225 to be replaced by a serine (S). 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
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MutPred
0.28
.;Loss of glycosylation at P225 (P = 0.1143);
MVP
MPC
1.9
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