17-47597321-A-T

Variant names:

• chr17-47597321-A-T
• rs8072100
• NM_006310.4:c.1536+859A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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]

KPNB1-DT (HGNC:55336): (KPNB1 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NPEPPS	NM_006310.4	c.1536+859A>T		intron_variant	Intron 13 of 22	ENST00000322157.9	NP_006301.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPEPPS	ENST00000322157.9	c.1536+859A>T		intron_variant	Intron 13 of 22	1	NM_006310.4	ENSP00000320324.4

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

African (AFR) AF: 0.489 AC: 20244 AN: 41430

American (AMR) AF: 0.624 AC: 9516 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.537 AC: 1863 AN: 3468

East Asian (EAS) AF: 0.660 AC: 3417 AN: 5178

South Asian (SAS) AF: 0.612 AC: 2953 AN: 4826

European-Finnish (FIN) AF: 0.537 AC: 5642 AN: 10502

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.520 AC: 35336 AN: 67952

Other (OTH) AF: 0.543 AC: 1146 AN: 2110

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
PhyloP100		0.84
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8072100; hg19: chr17-45674687;