17-47597321-A-T

Position:

• chr17-47597321-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006310.4(NPEPPS):​c.1536+859A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 151,928 control chromosomes in the GnomAD database, including 21,745 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.53 (21745 hom., cov: 31)
• Consequence: NPEPPS NM_006310.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.836

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPEPPS	NM_006310.4	c.1536+859A>T		intron_variant		ENST00000322157.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPEPPS	ENST00000322157.9	c.1536+859A>T		intron_variant		1	NM_006310.4	P1

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80740 AN: 151810 Hom.: 21725 Cov.: 31

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.659

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.542

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.532 AC: 80812 AN: 151928 Hom.: 21745 Cov.: 31 AF XY: 0.538 AC XY: 39936 AN XY: 74242

Gnomad4 AFR AF: 0.489

Gnomad4 AMR AF: 0.624

Gnomad4 ASJ AF: 0.537

Gnomad4 EAS AF: 0.660

Gnomad4 SAS AF: 0.612

Gnomad4 FIN AF: 0.537

Gnomad4 NFE AF: 0.520

Gnomad4 OTH AF: 0.543

Alfa AF: 0.400 Hom.: 1129

Bravo AF: 0.537

Asia WGS AF: 0.671 AC: 2333 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.5
DANN	Benign	0.58

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: rs8072100; hg19: chr17-45674687;