rs201212390

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006310.4(NPEPPS):​c.219C>G​(p.Asp73Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D73D) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 26)

Consequence

NPEPPS
NM_006310.4 missense

Scores

1
3
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.97
Variant links:
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.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.11947176).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NPEPPSNM_006310.4 linkc.219C>G p.Asp73Glu missense_variant Exon 1 of 23 ENST00000322157.9 NP_006301.3 P55786-1
NPEPPSNM_001411130.1 linkc.219C>G p.Asp73Glu missense_variant Exon 1 of 24 NP_001398059.1
NPEPPSNM_001330257.2 linkc.207C>G p.Asp69Glu missense_variant Exon 2 of 24 NP_001317186.1 P55786E9PLK3B7Z899
NPEPPSXM_017025373.1 linkc.207C>G p.Asp69Glu missense_variant Exon 2 of 25 XP_016880862.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NPEPPSENST00000322157.9 linkc.219C>G p.Asp73Glu missense_variant Exon 1 of 23 1 NM_006310.4 ENSP00000320324.4 P55786-1
NPEPPSENST00000526247.6 linkn.207C>G non_coding_transcript_exon_variant Exon 2 of 8 3 ENSP00000433735.1 E9PJF9

Frequencies

GnomAD3 genomes
Cov.:
26
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
26
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.31
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
22
DANN
Benign
0.97
DEOGEN2
Benign
0.069
.;.;T
Eigen
Benign
-0.59
Eigen_PC
Benign
-0.43
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Uncertain
0.91
D;D;D
M_CAP
Uncertain
0.11
D
MetaRNN
Benign
0.12
T;T;T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
-0.34
.;.;N
PrimateAI
Pathogenic
0.88
D
PROVEAN
Benign
0.57
N;N;N
REVEL
Benign
0.093
Sift
Benign
0.58
T;T;T
Sift4G
Benign
1.0
T;T;T
Polyphen
0.0
.;B;B
Vest4
0.24, 0.21
MutPred
0.36
.;.;Gain of catalytic residue at D73 (P = 0.0861);
MVP
0.043
MPC
1.7
ClinPred
0.84
D
GERP RS
2.7
Varity_R
0.12
gMVP
0.76

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs201212390; hg19: chr17-45608885; API