17-47531519-C-G

Variant names:

• chr17-47531519-C-G
• rs201212390
• NM_006310.4:c.219C>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.219C>G​(p.Asp73Glu) 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. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D73D) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 26)
• Consequence: NPEPPS NM_006310.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.97
• Publications: 1 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: 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=0.11947176).

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.219C>G	p.Asp73Glu	missense	Exon 1 of 23	NP_006301.3
	NPEPPS	NM_001411130.1		c.219C>G	p.Asp73Glu	missense	Exon 1 of 24	NP_001398059.1	A0A7I2V3W8
	NPEPPS	NM_001330257.2		c.207C>G	p.Asp69Glu	missense	Exon 2 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.219C>G	p.Asp73Glu	missense	Exon 1 of 23	ENSP00000320324.4	P55786-1
	NPEPPS	ENST00000526247.6	TSL:3	n.207C>G		non_coding_transcript_exon	Exon 2 of 8	ENSP00000433735.1	E9PJF9
	NPEPPS	ENST00000527298.5	TSL:1	n.219C>G		non_coding_transcript_exon	Exon 1 of 12	ENSP00000434585.1	E9PPD4

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 26

Alfa AF: 0.00 Hom.: 40

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.069	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.43
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.34	N
PhyloP100		6.0
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	0.57	N
REVEL	Benign	0.093
Sift	Benign	0.58	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.24
MutPred		0.36		Gain of catalytic residue at D73 (P = 0.0861)
MVP		0.043
MPC		1.7
ClinPred		0.84	D
GERP RS		2.7
PromoterAI		-0.066	Neutral
Varity_R		0.12
gMVP		0.76

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: rs201212390; hg19: chr17-45608885;