rs201212390

Variant names:

• chr17-47531519-C-G
• rs201212390
• NM_006310.4:c.219C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-47531519-C-G
• chr17-47531519-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. 12/21 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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11947176).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NPEPPS	NM_006310.4	c.219C>G	p.Asp73Glu	missense_variant	Exon 1 of 23	ENST00000322157.9	NP_006301.3
NPEPPS	NM_001411130.1	c.219C>G	p.Asp73Glu	missense_variant	Exon 1 of 24		NP_001398059.1
NPEPPS	NM_001330257.2	c.207C>G	p.Asp69Glu	missense_variant	Exon 2 of 24		NP_001317186.1
NPEPPS	XM_017025373.1	c.207C>G	p.Asp69Glu	missense_variant	Exon 2 of 25		XP_016880862.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPEPPS	ENST00000322157.9	c.219C>G	p.Asp73Glu	missense_variant	Exon 1 of 23	1	NM_006310.4	ENSP00000320324.4
NPEPPS	ENST00000526247.6	n.207C>G		non_coding_transcript_exon_variant	Exon 2 of 8	3		ENSP00000433735.1

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 26

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.12	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-0.34	.;.;N
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	0.57	N;N;N
REVEL	Benign	0.093
Sift	Benign	0.58	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	.;B;B
Vest4		0.24, 0.21
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
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

Publications

LitVar

Other links and lift over

dbSNP: rs201212390; hg19: chr17-45608885;