17-47530206-T-G

Position:

• chr17-47530206-T-G

Variant summary

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

The NM_001330257.2(NPEPPS):​c.78-1184T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 144,964 control chromosomes in the GnomAD database, including 19,486 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 0.51 (19486 hom., cov: 22)
• Consequence: NPEPPS NM_001330257.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.296

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]

NPEPPS (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPEPPS	NM_001330257.2	c.78-1184T>G		intron_variant			NP_001317186.1
NPEPPS	XM_017025373.1	c.78-1184T>G		intron_variant			XP_016880862.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPEPPS	ENST00000526247.6	n.78-1184T>G		intron_variant		3		ENSP00000433735.1

Frequencies

GnomAD3 genomes AF: 0.511 AC: 73971 AN: 144856 Hom.: 19472 Cov.: 22

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.657

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.603

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.534

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

GnomAD4 genome AF: 0.511 AC: 74028 AN: 144964 Hom.: 19486 Cov.: 22 AF XY: 0.516 AC XY: 36317 AN XY: 70354

Gnomad4 AFR AF: 0.410

Gnomad4 AMR AF: 0.622

Gnomad4 ASJ AF: 0.537

Gnomad4 EAS AF: 0.658

Gnomad4 SAS AF: 0.608

Gnomad4 FIN AF: 0.525

Gnomad4 NFE AF: 0.524

Gnomad4 OTH AF: 0.535

Alfa AF: 0.509 Hom.: 2526

Bravo AF: 0.515

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.9
DANN	Benign	0.84

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2935183; hg19: chr17-45607572; COSMIC: COSV59105493; COSMIC: COSV59105493;