17-47531409-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006310.4(NPEPPS):​c.109C>G​(p.Leu37Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000066 in 151,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L37F) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 26)
Exomes š‘“: 7.2e-7 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

NPEPPS
NM_006310.4 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.09
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.066096306).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NPEPPSNM_006310.4 linkc.109C>G p.Leu37Val missense_variant Exon 1 of 23 ENST00000322157.9 NP_006301.3 P55786-1
NPEPPSNM_001411130.1 linkc.109C>G p.Leu37Val missense_variant Exon 1 of 24 NP_001398059.1
NPEPPSNM_001330257.2 linkc.97C>G p.Leu33Val missense_variant Exon 2 of 24 NP_001317186.1 P55786E9PLK3B7Z899
NPEPPSXM_017025373.1 linkc.97C>G p.Leu33Val 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.109C>G p.Leu37Val missense_variant Exon 1 of 23 1 NM_006310.4 ENSP00000320324.4 P55786-1
NPEPPSENST00000526247.6 linkn.97C>G non_coding_transcript_exon_variant Exon 2 of 8 3 ENSP00000433735.1 E9PJF9

Frequencies

GnomAD3 genomes
AF:
0.00000660
AC:
1
AN:
151426
Hom.:
0
Cov.:
26
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000682
AC:
1
AN:
146546
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
78840
show subpopulations
Gnomad AFR exome
AF:
0.000146
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
7.16e-7
AC:
1
AN:
1395700
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
688432
show subpopulations
Gnomad4 AFR exome
AF:
0.0000318
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000660
AC:
1
AN:
151532
Hom.:
0
Cov.:
26
AF XY:
0.0000135
AC XY:
1
AN XY:
74034
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.079
BayesDel_addAF
Benign
-0.45
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
20
DANN
Benign
0.97
DEOGEN2
Benign
0.16
.;T
Eigen
Benign
-0.54
Eigen_PC
Benign
-0.41
FATHMM_MKL
Benign
0.36
N
LIST_S2
Benign
0.57
T;T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.066
T;T
MetaSVM
Benign
-0.86
T
MutationAssessor
Benign
-0.20
.;N
PrimateAI
Pathogenic
0.88
D
PROVEAN
Benign
-0.060
N;N
REVEL
Benign
0.055
Sift
Benign
0.035
D;T
Sift4G
Benign
0.12
T;T
Polyphen
0.024
B;B
Vest4
0.068
MutPred
0.31
.;Loss of helix (P = 0.028);
MVP
0.12
MPC
1.8
ClinPred
0.040
T
GERP RS
2.5
Varity_R
0.091
gMVP
0.52

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: rs778878338; hg19: chr17-45608775; API