chr17-47590838-G-A
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2
The NM_006310.4(NPEPPS):c.1217G>A(p.Arg406His) variant causes a missense change. The variant allele was found at a frequency of 0.0000193 in 1,604,094 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: 0.000020 ( 0 hom. )
Consequence
NPEPPS
NM_006310.4 missense
NM_006310.4 missense
Scores
4
7
6
Clinical Significance
Conservation
PhyloP100: 6.61
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 Likely_benign. Variant got -3 ACMG points.
PP2
Missense variant where missense usually causes diseases, NPEPPS
BS2
High AC in GnomAdExome4 at 29 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NPEPPS | NM_006310.4 | c.1217G>A | p.Arg406His | missense_variant | 10/23 | ENST00000322157.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NPEPPS | ENST00000322157.9 | c.1217G>A | p.Arg406His | missense_variant | 10/23 | 1 | NM_006310.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151982Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000243 AC: 6AN: 247036Hom.: 0 AF XY: 0.00000746 AC XY: 1AN XY: 134078
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GnomAD4 exome AF: 0.0000200 AC: 29AN: 1451994Hom.: 0 Cov.: 30 AF XY: 0.0000208 AC XY: 15AN XY: 720744
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152100Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74346
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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 | Dec 09, 2023 | The c.1217G>A (p.R406H) alteration is located in exon 10 (coding exon 10) of the NPEPPS gene. This alteration results from a G to A substitution at nucleotide position 1217, causing the arginine (R) at amino acid position 406 to be replaced by a histidine (H). 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
Pathogenic
DANN
Pathogenic
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
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
Pathogenic
D
PROVEAN
Uncertain
D;D;D;D
REVEL
Benign
Sift
Uncertain
D;D;T;T
Sift4G
Uncertain
D;D;T;T
Polyphen
D;D;.;.
Vest4
MutPred
0.54
.;Gain of disorder (P = 0.0983);.;.;
MVP
MPC
2.3
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