17-47531382-G-C

Variant names:

• chr17-47531382-G-C
• rs1907751929
• NM_006310.4:c.82G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_006310.4(NPEPPS):​c.82G>C​(p.Val28Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 26)
  • Failed GnomAD Quality Control
• Consequence: NPEPPS NM_006310.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.935
• 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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054567605).
• BP6: Variant 17-47531382-G-C is Benign according to our data. Variant chr17-47531382-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2569413.Status of the report is criteria_provided_single_submitter, 1 stars.

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.82G>C	p.Val28Leu	missense	Exon 1 of 23	NP_006301.3
	NPEPPS	NM_001411130.1		c.82G>C	p.Val28Leu	missense	Exon 1 of 24	NP_001398059.1	A0A7I2V3W8
	NPEPPS	NM_001330257.2		c.78-8G>C		splice_region intron	N/A	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.82G>C	p.Val28Leu	missense	Exon 1 of 23	ENSP00000320324.4	P55786-1
	NPEPPS	ENST00000527298.5	TSL:1	n.82G>C		non_coding_transcript_exon	Exon 1 of 12	ENSP00000434585.1	E9PPD4
	NPEPPS	ENST00000526247.6	TSL:3	n.78-8G>C		splice_region intron	N/A	ENSP00000433735.1	E9PJF9

Frequencies

GnomAD3 genomes AF: 0.00000668 AC: 1 AN: 149676 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000664

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000668 AC: 1 AN: 149676 Hom.: 0 Cov.: 26 AF XY: 0.0000137 AC XY: 1 AN XY: 72978

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 40596

American (AMR) AF: 0.0000664 AC: 1 AN: 15052

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5012

South Asian (SAS) AF: 0.00 AC: 0 AN: 4684

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10240

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67376

Other (OTH) AF: 0.00 AC: 0 AN: 2046

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.086
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	15
DANN	Benign	0.39
DEOGEN2	Benign	0.18	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.94
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	0.030	N
REVEL	Benign	0.051
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.069
MutPred		0.37		Loss of sheet (P = 0.0181)
MVP		0.068
MPC		1.8
ClinPred		0.034	T
GERP RS		0.36
PromoterAI		0.025	Neutral
Varity_R		0.042
gMVP		0.46

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: rs1907751929; hg19: chr17-45608748; COSMIC: COSV59105532; COSMIC: COSV59105532;