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GeneBe

17-47587239-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_006310.4(NPEPPS):c.990A>G(p.Ala330=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00081 in 1,580,556 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0041 ( 2 hom., cov: 30)
Exomes 𝑓: 0.00046 ( 5 hom. )

Consequence

NPEPPS
NM_006310.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.403
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 -15 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=-0.51).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 17-47587239-A-G is Benign according to our data. Variant chr17-47587239-A-G is described in ClinVar as [Benign]. Clinvar id is 780444.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=-0.403 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000461 (659/1430696) while in subpopulation AFR AF= 0.0179 (572/31896). AF 95% confidence interval is 0.0167. There are 5 homozygotes in gnomad4_exome. There are 299 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.
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 621 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NPEPPSNM_006310.4 linkuse as main transcriptc.990A>G p.Ala330= synonymous_variant 9/23 ENST00000322157.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NPEPPSENST00000322157.9 linkuse as main transcriptc.990A>G p.Ala330= synonymous_variant 9/231 NM_006310.4 P1P55786-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00415
AC:
621
AN:
149744
Hom.:
2
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.0148
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00114
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:
0.0000443
Gnomad OTH
AF:
0.00145
GnomAD3 exomes
AF:
0.00108
AC:
246
AN:
228758
Hom.:
3
AF XY:
0.000913
AC XY:
113
AN XY:
123744
show subpopulations
Gnomad AFR exome
AF:
0.0150
Gnomad AMR exome
AF:
0.000443
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000745
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000291
Gnomad OTH exome
AF:
0.000713
GnomAD4 exome
AF:
0.000461
AC:
659
AN:
1430696
Hom.:
5
Cov.:
33
AF XY:
0.000421
AC XY:
299
AN XY:
710208
show subpopulations
Gnomad4 AFR exome
AF:
0.0179
Gnomad4 AMR exome
AF:
0.000483
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000254
Gnomad4 SAS exome
AF:
0.0000376
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000364
Gnomad4 OTH exome
AF:
0.00103
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00414
AC:
621
AN:
149860
Hom.:
2
Cov.:
30
AF XY:
0.00383
AC XY:
280
AN XY:
73060
show subpopulations
Gnomad4 AFR
AF:
0.0147
Gnomad4 AMR
AF:
0.00114
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000444
Gnomad4 OTH
AF:
0.00144
Alfa
AF:
0.00107
Hom.:
0
Bravo
AF:
0.00509

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 testingInvitaeJun 27, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.51
Cadd
Benign
10
Dann
Benign
0.70
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs372187657; hg19: chr17-45664605; API