Genetic Variant NPEPPS:p.Leu40Leu (chr17-47531418-C-T) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_006310.4(NPEPPS):c.118C>T(p.Leu40Leu) 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

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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]

NPEPPS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

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_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.742 with no splicing effect.

BS2

High AC in GnomAd4 at 873 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPEPPS	NM_006310.4 link	c.118C>T	p.Leu40Leu	synonymous_variant	Exon 1 of 23	ENST00000322157.9	NP_006301.3	P55786-1
NPEPPS	NM_001411130.1 link	c.118C>T	p.Leu40Leu	synonymous_variant	Exon 1 of 24		NP_001398059.1
NPEPPS	NM_001330257.2 link	c.106C>T	p.Leu36Leu	synonymous_variant	Exon 2 of 24		NP_001317186.1	P55786E9PLK3B7Z899
NPEPPS	XM_017025373.1 link	c.106C>T	p.Leu36Leu	synonymous_variant	Exon 2 of 25		XP_016880862.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPEPPS	ENST00000322157.9 link	c.118C>T	p.Leu40Leu	synonymous_variant	Exon 1 of 23	1	NM_006310.4	ENSP00000320324.4		P55786-1
NPEPPS	ENST00000526247.6 link	n.106C>T		non_coding_transcript_exon_variant	Exon 2 of 8	3		ENSP00000433735.1		E9PJF9

Frequencies

GnomAD3 genomes

AF:

0.00577

AC:

874

AN:

151526

Hom.:

Cov.:

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.:

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.:

Cov.:

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

AF:

0.00576

AC:

873

AN:

151630

Hom.:

Cov.:

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.:

Bravo

AF:

0.00470

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 26, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over