17-47601671-C-G

Variant names:

• chr17-47601671-C-G
• NM_006310.4:c.1664C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006310.4(NPEPPS):​c.1664C>G​(p.Ala555Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: NPEPPS NM_006310.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.14
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13123786).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006310.4. 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_006310.4	MANE Select	c.1664C>G	p.Ala555Gly	missense	Exon 15 of 23	NP_006301.3
	NPEPPS	NM_001411130.1		c.1664C>G	p.Ala555Gly	missense	Exon 15 of 24	NP_001398059.1	A0A7I2V3W8
	NPEPPS	NM_001330257.2		c.1652C>G	p.Ala551Gly	missense	Exon 16 of 24	NP_001317186.1	E9PLK3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPEPPS	ENST00000322157.9	TSL:1 MANE Select	c.1664C>G	p.Ala555Gly	missense	Exon 15 of 23	ENSP00000320324.4	P55786-1
	NPEPPS	ENST00000677370.1		c.1664C>G	p.Ala555Gly	missense	Exon 15 of 24	ENSP00000503738.1	A0A7I2V3W8
	NPEPPS	ENST00000677120.1		c.1664C>G	p.Ala555Gly	missense	Exon 15 of 24	ENSP00000503682.1	P55786-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.066
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	1.1	L
PhyloP100		4.1
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.13
Sift	Benign	0.34	T
Sift4G	Benign	0.50	T
Polyphen		0.0	B
Vest4		0.20
MutPred		0.34		Gain of disorder (P = 0.0703)
MVP		0.19
MPC		0.59
ClinPred		0.55	D
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.079
gMVP		0.42

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

hg19: chr17-45679037;