chr17-47531519-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006310.4(NPEPPS):​c.219C>T​(p.Asp73Asp) variant causes a synonymous change. The variant allele was found at a frequency of 0.0539 in 1,608,402 control chromosomes in the GnomAD database, including 2,729 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.047 (226 hom., cov: 26)
  • Exomes 𝑓: 0.055 (2503 hom.)
• Consequence: NPEPPS NM_006310.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 17-47531519-C-T is Benign according to our data. Variant chr17-47531519-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 771497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0625 is higher than 0.05.

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>T	p.Asp73Asp	synonymous	Exon 1 of 23	NP_006301.3
	NPEPPS	NM_001411130.1		c.219C>T	p.Asp73Asp	synonymous	Exon 1 of 24	NP_001398059.1	A0A7I2V3W8
	NPEPPS	NM_001330257.2		c.207C>T	p.Asp69Asp	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.219C>T	p.Asp73Asp	synonymous	Exon 1 of 23	ENSP00000320324.4	P55786-1
	NPEPPS	ENST00000526247.6	TSL:3	n.207C>T		non_coding_transcript_exon	Exon 2 of 8	ENSP00000433735.1	E9PJF9
	NPEPPS	ENST00000527298.5	TSL:1	n.219C>T		non_coding_transcript_exon	Exon 1 of 12	ENSP00000434585.1	E9PPD4

Frequencies

GnomAD3 genomes AF: 0.0467 AC: 7088 AN: 151912 Hom.: 226 Cov.: 26

Gnomad AFR AF: 0.0219

Gnomad AMI AF: 0.0538

Gnomad AMR AF: 0.0545

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0251

Gnomad FIN AF: 0.0270

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0640

Gnomad OTH AF: 0.0616

GnomAD2 exomes AF: 0.0467 AC: 11130 AN: 238404 AF XY: 0.0479

Gnomad AFR exome AF: 0.0194

Gnomad AMR exome AF: 0.0359

Gnomad ASJ exome AF: 0.104

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0310

Gnomad NFE exome AF: 0.0648

Gnomad OTH exome AF: 0.0595

GnomAD4 exome AF: 0.0547 AC: 79656 AN: 1456380 Hom.: 2503 Cov.: 33 AF XY: 0.0545 AC XY: 39467 AN XY: 724274

African (AFR) AF: 0.0201 AC: 669 AN: 33336

American (AMR) AF: 0.0393 AC: 1744 AN: 44408

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 2669 AN: 26064

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39528

South Asian (SAS) AF: 0.0262 AC: 2246 AN: 85744

European-Finnish (FIN) AF: 0.0323 AC: 1704 AN: 52736

Middle Eastern (MID) AF: 0.113 AC: 472 AN: 4174

European-Non Finnish (NFE) AF: 0.0601 AC: 66726 AN: 1110358

Other (OTH) AF: 0.0570 AC: 3421 AN: 60032

GnomAD4 genome AF: 0.0467 AC: 7094 AN: 152022 Hom.: 226 Cov.: 26 AF XY: 0.0445 AC XY: 3308 AN XY: 74310

African (AFR) AF: 0.0219 AC: 911 AN: 41530

American (AMR) AF: 0.0545 AC: 833 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 369 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5144

South Asian (SAS) AF: 0.0253 AC: 122 AN: 4826

European-Finnish (FIN) AF: 0.0270 AC: 285 AN: 10548

Middle Eastern (MID) AF: 0.158 AC: 46 AN: 292

European-Non Finnish (NFE) AF: 0.0641 AC: 4351 AN: 67916

Other (OTH) AF: 0.0610 AC: 128 AN: 2100

Alfa AF: 0.0402 Hom.: 40

Bravo AF: 0.0484

ClinVar

ClinVar submissions

Significance: Likely 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	-0.52
CADD	Benign	15
DANN	Benign	0.94
PhyloP100		6.0
PromoterAI		-0.0088	Neutral
Mutation Taster		=88/12	polymorphism (auto)

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; COSMIC: COSV59100645;