Genetic Variant NPEPPS:p.Asp73Asp (chr17-47531519-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006310.4(NPEPPS):c.219C>T(p.Asp73Asp) variant causes a synonymous change. The variant allele was found at a frequency of 0.0539 in 1,608,402 control chromosomes in the GnomAD database, including 2,729 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.047 ( 226 hom., cov: 26)

Exomes 𝑓: 0.055 ( 2503 hom. )

Consequence

NPEPPS
NM_006310.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

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]

NPEPPS links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 17-47531519-C-T is Benign according to our data. Variant chr17-47531519-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 771497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPEPPS	NM_006310.4 link	c.219C>T	p.Asp73Asp	synonymous_variant	Exon 1 of 23	ENST00000322157.9	NP_006301.3	P55786-1
NPEPPS	NM_001411130.1 link	c.219C>T	p.Asp73Asp	synonymous_variant	Exon 1 of 24		NP_001398059.1
NPEPPS	NM_001330257.2 link	c.207C>T	p.Asp69Asp	synonymous_variant	Exon 2 of 24		NP_001317186.1	P55786E9PLK3B7Z899
NPEPPS	XM_017025373.1 link	c.207C>T	p.Asp69Asp	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.219C>T	p.Asp73Asp	synonymous_variant	Exon 1 of 23	1	NM_006310.4	ENSP00000320324.4		P55786-1
NPEPPS	ENST00000526247.6 link	n.207C>T		non_coding_transcript_exon_variant	Exon 2 of 8	3		ENSP00000433735.1		E9PJF9

Frequencies

GnomAD3 genomes

AF:

0.0467

AC:

7088

AN:

151912

Hom.:

226

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0219

Gnomad AMI

AF:

0.0538

Gnomad AMR

AF:

0.0545

Gnomad ASJ

AF:

0.107

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0251

Gnomad FIN

AF:

0.0270

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.0640

Gnomad OTH

AF:

0.0616

GnomAD3 exomes

AF:

0.0467

AC:

11130

AN:

238404

Hom.:

370

AF XY:

0.0479

AC XY:

6233

AN XY:

130182

show subpopulations

Gnomad AFR exome

AF:

0.0194

Gnomad AMR exome

AF:

0.0359

Gnomad ASJ exome

AF:

0.104

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0240

Gnomad FIN exome

AF:

0.0310

Gnomad NFE exome

AF:

0.0648

Gnomad OTH exome

AF:

0.0595

GnomAD4 exome

AF:

0.0547

AC:

79656

AN:

1456380

Hom.:

2503

Cov.:

AF XY:

0.0545

AC XY:

39467

AN XY:

724274

show subpopulations

Gnomad4 AFR exome

AF:

0.0201

Gnomad4 AMR exome

AF:

0.0393

Gnomad4 ASJ exome

AF:

0.102

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0262

Gnomad4 FIN exome

AF:

0.0323

Gnomad4 NFE exome

AF:

0.0601

Gnomad4 OTH exome

AF:

0.0570

GnomAD4 genome

AF:

0.0467

AC:

7094

AN:

152022

Hom.:

226

Cov.:

AF XY:

0.0445

AC XY:

3308

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.0219

Gnomad4 AMR

AF:

0.0545

Gnomad4 ASJ

AF:

0.107

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0253

Gnomad4 FIN

AF:

0.0270

Gnomad4 NFE

AF:

0.0641

Gnomad4 OTH

AF:

0.0610

Alfa

AF:

0.0402

Hom.:

Bravo

AF:

0.0484

ClinVar

Significance: Likely 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: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely 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

-0.52

CADD

Benign

DANN

Benign

0.94

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