17-47590709-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_006310.4(NPEPPS):c.1096-8G>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000424 in 1,609,198 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0025 (3 hom., cov: 31)
  • Exomes 𝑓: 0.00021 (1 hom.)
• Consequence: NPEPPS NM_006310.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00004243
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.39

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 17-47590709-G-C is Benign according to our data. Variant chr17-47590709-G-C is described in ClinVar as [Benign]. Clinvar id is 710465.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 375 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPEPPS	NM_006310.4	c.1096-8G>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000322157.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPEPPS	ENST00000322157.9	c.1096-8G>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_006310.4	P1

Frequencies

GnomAD3 genomes AF: 0.00246 AC: 375 AN: 152152 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.00871

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

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: 0.000479

GnomAD3 exomes AF: 0.000561 AC: 138 AN: 245832 Hom.: 0 AF XY: 0.000405 AC XY: 54 AN XY: 133438

Gnomad AFR exome AF: 0.00824

Gnomad AMR exome AF: 0.000267

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: 0.000335

GnomAD4 exome AF: 0.000207 AC: 302 AN: 1456928 Hom.: 1 Cov.: 30 AF XY: 0.000150 AC XY: 109 AN XY: 724354

Gnomad4 AFR exome AF: 0.00763

Gnomad4 AMR exome AF: 0.000296

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: 0.00000270

Gnomad4 OTH exome AF: 0.000515

GnomAD4 genome AF: 0.00250 AC: 380 AN: 152270 Hom.: 3 Cov.: 31 AF XY: 0.00227 AC XY: 169 AN XY: 74444

Gnomad4 AFR AF: 0.00881

Gnomad4 AMR AF: 0.000850

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: 0.000474

Alfa AF: 0.00101 Hom.: 0

Bravo AF: 0.00283

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 13, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	1.3
Dann	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000042
dbscSNV1_RF	Benign	0.0020
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

Other links and lift over

dbSNP: rs200948229; hg19: chr17-45668075;