chr17-47531418-C-T

Variant names:

• chr17-47531418-C-T
• rs200065879
• NM_006310.4:c.118C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_006310.4(NPEPPS):​c.118C>T​(p.Leu40Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00747 in 1,547,558 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0058 (6 hom., cov: 26)
  • Exomes 𝑓: 0.0077 (54 hom.)
• Consequence: NPEPPS NM_006310.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.742
• 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: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 17-47531418-C-T is Benign according to our data. Variant chr17-47531418-C-T is described in ClinVar as Benign. ClinVar VariationId is 789229.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.742 with no splicing effect.
• BS2: High AC in GnomAd4 at 873 AD gene.

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.118C>T	p.Leu40Leu	synonymous	Exon 1 of 23	NP_006301.3
	NPEPPS	NM_001411130.1		c.118C>T	p.Leu40Leu	synonymous	Exon 1 of 24	NP_001398059.1	A0A7I2V3W8
	NPEPPS	NM_001330257.2		c.106C>T	p.Leu36Leu	synonymous	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.118C>T	p.Leu40Leu	synonymous	Exon 1 of 23	ENSP00000320324.4	P55786-1
	NPEPPS	ENST00000526247.6	TSL:3	n.106C>T		non_coding_transcript_exon	Exon 2 of 8	ENSP00000433735.1	E9PJF9
	NPEPPS	ENST00000527298.5	TSL:1	n.118C>T		non_coding_transcript_exon	Exon 1 of 12	ENSP00000434585.1	E9PPD4

Frequencies

GnomAD3 genomes AF: 0.00577 AC: 874 AN: 151526 Hom.: 6 Cov.: 26

Gnomad AFR AF: 0.00191

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00341

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00459

Gnomad FIN AF: 0.0175

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.00777

Gnomad OTH AF: 0.00384

GnomAD2 exomes AF: 0.00584 AC: 863 AN: 147736 AF XY: 0.00570

Gnomad AFR exome AF: 0.00218

Gnomad AMR exome AF: 0.00282

Gnomad ASJ exome AF: 0.000239

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0164

Gnomad NFE exome AF: 0.00758

Gnomad OTH exome AF: 0.00727

GnomAD4 exome AF: 0.00765 AC: 10680 AN: 1395928 Hom.: 54 Cov.: 33 AF XY: 0.00744 AC XY: 5126 AN XY: 688548

African (AFR) AF: 0.00143 AC: 45 AN: 31498

American (AMR) AF: 0.00280 AC: 100 AN: 35680

Ashkenazi Jewish (ASJ) AF: 0.000437 AC: 11 AN: 25152

East Asian (EAS) AF: 0.0000560 AC: 2 AN: 35696

South Asian (SAS) AF: 0.00387 AC: 306 AN: 79130

European-Finnish (FIN) AF: 0.0177 AC: 856 AN: 48466

Middle Eastern (MID) AF: 0.00344 AC: 14 AN: 4066

European-Non Finnish (NFE) AF: 0.00835 AC: 9007 AN: 1078460

Other (OTH) AF: 0.00587 AC: 339 AN: 57780

GnomAD4 genome AF: 0.00576 AC: 873 AN: 151630 Hom.: 6 Cov.: 26 AF XY: 0.00606 AC XY: 449 AN XY: 74088

African (AFR) AF: 0.00191 AC: 79 AN: 41438

American (AMR) AF: 0.00341 AC: 52 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5088

South Asian (SAS) AF: 0.00459 AC: 22 AN: 4790

European-Finnish (FIN) AF: 0.0175 AC: 183 AN: 10476

Middle Eastern (MID) AF: 0.00690 AC: 2 AN: 290

European-Non Finnish (NFE) AF: 0.00777 AC: 527 AN: 67816

Other (OTH) AF: 0.00380 AC: 8 AN: 2108

Alfa AF: 0.00509 Hom.: 3

Bravo AF: 0.00470

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	11
DANN	Benign	0.96
PhyloP100		0.74
PromoterAI		0.032	Neutral
Mutation Taster		=100/0	polymorphism

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: rs200065879; hg19: chr17-45608784; COSMIC: COSV59106398;