chr17-47530206-T-G

Variant names:

• chr17-47530206-T-G
• rs2935183
• ENST00000526247.6:n.78-1184T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330257.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPEPPS	NM_001330257.2		c.78-1184T>G		intron	N/A	NP_001317186.1	E9PLK3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPEPPS	ENST00000526247.6	TSL:3	n.78-1184T>G		intron	N/A	ENSP00000433735.1	E9PJF9
	NPEPPS	ENST00000530173.6	TSL:2	c.78-1184T>G		intron	N/A	ENSP00000433287.1	E9PLK3
	NPEPPS	ENST00000525007.5	TSL:3	c.78-1211T>G		intron	N/A	ENSP00000437019.1	E9PP11

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

African (AFR) AF: 0.410 AC: 16197 AN: 39522

American (AMR) AF: 0.622 AC: 8983 AN: 14452

Ashkenazi Jewish (ASJ) AF: 0.537 AC: 1836 AN: 3422

East Asian (EAS) AF: 0.658 AC: 3177 AN: 4828

South Asian (SAS) AF: 0.608 AC: 2752 AN: 4530

European-Finnish (FIN) AF: 0.525 AC: 4950 AN: 9422

Middle Eastern (MID) AF: 0.607 AC: 170 AN: 280

European-Non Finnish (NFE) AF: 0.524 AC: 34411 AN: 65682

Other (OTH) AF: 0.535 AC: 1056 AN: 1974

Alfa AF: 0.509 Hom.: 2526

Bravo AF: 0.515

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.9
DANN	Benign	0.84
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

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