17-47531519-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006310.4(NPEPPS):c.219C>T(p.Asp73=) 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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.97

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=-0.52).
• 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_single_submitter, 1 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/exons	MANE	UniProt
NPEPPS	NM_006310.4	c.219C>T	p.Asp73=	synonymous_variant	1/23	ENST00000322157.9
NPEPPS	NM_001411130.1	c.219C>T	p.Asp73=	synonymous_variant	1/24
NPEPPS	NM_001330257.2	c.207C>T	p.Asp69=	synonymous_variant	2/24
NPEPPS	XM_017025373.1	c.207C>T	p.Asp69=	synonymous_variant	2/25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPEPPS	ENST00000322157.9	c.219C>T	p.Asp73=	synonymous_variant	1/23	1	NM_006310.4	P1

Frequencies

GnomAD3 genomes AF: 0.0467 AC: 7088 AN: 151912 Hom.: 226 Cov.: 26

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

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.: 33 AF XY: 0.0545 AC XY: 39467 AN XY: 724274

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.: 26 AF XY: 0.0445 AC XY: 3308 AN XY: 74310

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.: 40

Bravo AF: 0.0484

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	15
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

Other links and lift over

dbSNP: rs201212390; hg19: chr17-45608885; COSMIC: COSV59100645;