17-47587320-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_006310.4(NPEPPS):c.1071A>G(p.Gln357=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00154 in 1,604,692 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0071 (15 hom., cov: 29)
  • Exomes 𝑓: 0.00096 (15 hom.)
• Consequence: NPEPPS NM_006310.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.41

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 17-47587320-A-G is Benign according to our data. Variant chr17-47587320-A-G is described in ClinVar as [Benign]. Clinvar id is 786652.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00706 (1071/151732) while in subpopulation AFR AF= 0.0229 (947/41318). AF 95% confidence interval is 0.0217. There are 15 homozygotes in gnomad4. There are 475 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
• BS2: High AC in GnomAd at 1067 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPEPPS	NM_006310.4	c.1071A>G	p.Gln357=	synonymous_variant	9/23	ENST00000322157.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPEPPS	ENST00000322157.9	c.1071A>G	p.Gln357=	synonymous_variant	9/23	1	NM_006310.4	P1

Frequencies

GnomAD3 genomes AF: 0.00704 AC: 1067 AN: 151616 Hom.: 14 Cov.: 29

Gnomad AFR AF: 0.0229

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00573

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000280

Gnomad OTH AF: 0.00720

GnomAD3 exomes AF: 0.00223 AC: 534 AN: 239432 Hom.: 2 AF XY: 0.00178 AC XY: 231 AN XY: 129790

Gnomad AFR exome AF: 0.0224

Gnomad AMR exome AF: 0.00349

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000175

Gnomad SAS exome AF: 0.000108

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000520

Gnomad OTH exome AF: 0.00241

GnomAD4 exome AF: 0.000965 AC: 1402 AN: 1452960 Hom.: 15 Cov.: 33 AF XY: 0.000897 AC XY: 648 AN XY: 722460

Gnomad4 AFR exome AF: 0.0231

Gnomad4 AMR exome AF: 0.00377

Gnomad4 ASJ exome AF: 0.0000385

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.000131

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000252

Gnomad4 OTH exome AF: 0.00240

GnomAD4 genome AF: 0.00706 AC: 1071 AN: 151732 Hom.: 15 Cov.: 29 AF XY: 0.00640 AC XY: 475 AN XY: 74168

Gnomad4 AFR AF: 0.0229

Gnomad4 AMR AF: 0.00572

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000280

Gnomad4 OTH AF: 0.00713

Alfa AF: 0.00237 Hom.: 1

Bravo AF: 0.00822

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	-0.49
Cadd	Benign	8.3
Dann	Benign	0.67
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

Other links and lift over

dbSNP: rs145829042; hg19: chr17-45664686;