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GeneBe

17-47531418-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_006310.4(NPEPPS):c.118C>T(p.Leu40=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00747 in 1,547,558 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0058 ( 6 hom., cov: 26)
Exomes 𝑓: 0.0077 ( 54 hom. )

Consequence

NPEPPS
NM_006310.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.742
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 Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 17-47531418-C-T is Benign according to our data. Variant chr17-47531418-C-T is described in ClinVar as [Benign]. Clinvar id is 789229.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.742 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 874 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NPEPPSNM_006310.4 linkuse as main transcriptc.118C>T p.Leu40= synonymous_variant 1/23 ENST00000322157.9
NPEPPSNM_001411130.1 linkuse as main transcriptc.118C>T p.Leu40= synonymous_variant 1/24
NPEPPSNM_001330257.2 linkuse as main transcriptc.106C>T p.Leu36= synonymous_variant 2/24
NPEPPSXM_017025373.1 linkuse as main transcriptc.106C>T p.Leu36= synonymous_variant 2/25

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NPEPPSENST00000322157.9 linkuse as main transcriptc.118C>T p.Leu40= synonymous_variant 1/231 NM_006310.4 P1P55786-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00577
AC:
874
AN:
151526
Hom.:
6
Cov.:
26
show subpopulations
Gnomad AFR
AF:
0.00191
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00341
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00459
Gnomad FIN
AF:
0.0175
Gnomad MID
AF:
0.00955
Gnomad NFE
AF:
0.00777
Gnomad OTH
AF:
0.00384
GnomAD3 exomes
AF:
0.00584
AC:
863
AN:
147736
Hom.:
8
AF XY:
0.00570
AC XY:
453
AN XY:
79452
show subpopulations
Gnomad AFR exome
AF:
0.00218
Gnomad AMR exome
AF:
0.00282
Gnomad ASJ exome
AF:
0.000239
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00331
Gnomad FIN exome
AF:
0.0164
Gnomad NFE exome
AF:
0.00758
Gnomad OTH exome
AF:
0.00727
GnomAD4 exome
AF:
0.00765
AC:
10680
AN:
1395928
Hom.:
54
Cov.:
33
AF XY:
0.00744
AC XY:
5126
AN XY:
688548
show subpopulations
Gnomad4 AFR exome
AF:
0.00143
Gnomad4 AMR exome
AF:
0.00280
Gnomad4 ASJ exome
AF:
0.000437
Gnomad4 EAS exome
AF:
0.0000560
Gnomad4 SAS exome
AF:
0.00387
Gnomad4 FIN exome
AF:
0.0177
Gnomad4 NFE exome
AF:
0.00835
Gnomad4 OTH exome
AF:
0.00587
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00576
AC:
873
AN:
151630
Hom.:
6
Cov.:
26
AF XY:
0.00606
AC XY:
449
AN XY:
74088
show subpopulations
Gnomad4 AFR
AF:
0.00191
Gnomad4 AMR
AF:
0.00341
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00459
Gnomad4 FIN
AF:
0.0175
Gnomad4 NFE
AF:
0.00777
Gnomad4 OTH
AF:
0.00380
Alfa
AF:
0.00509
Hom.:
3
Bravo
AF:
0.00470

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJul 26, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.50
Cadd
Benign
11
Dann
Benign
0.96

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: rs200065879; hg19: chr17-45608784; COSMIC: COSV59106398; API