rs623980

Variant names:

• chr10-109886389-A-G
• rs623980
• NM_020383.4:c.653-48T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-109886389-A-G
• chr10-109886389-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020383.4(XPNPEP1):​c.653-48T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 1,574,810 control chromosomes in the GnomAD database, including 251,906 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.50 (19736 hom., cov: 33)
  • Exomes 𝑓: 0.56 (232170 hom.)
• Consequence: XPNPEP1 NM_020383.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 13 publications found

Genes affected

XPNPEP1 (HGNC:12822): (X-prolyl aminopeptidase 1) This gene encodes the cytosolic form of a metalloaminopeptidase that catalyzes the cleavage of the N-terminal amino acid adjacent to a proline residue. The gene product may play a role in degradation and maturation of tachykinins, neuropeptides, and peptide hormones. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Nov 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020383.4. 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
	XPNPEP1	NM_020383.4	MANE Select	c.653-48T>C		intron	N/A	NP_065116.3
	XPNPEP1	NM_001324133.2		c.653-48T>C		intron	N/A	NP_001311062.1
	XPNPEP1	NM_001324136.1		c.638-48T>C		intron	N/A	NP_001311065.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XPNPEP1	ENST00000502935.6	TSL:1 MANE Select	c.653-48T>C		intron	N/A	ENSP00000421566.1	Q9NQW7-3
	XPNPEP1	ENST00000322238.12	TSL:1	c.653-48T>C		intron	N/A	ENSP00000324011.8	Q9NQW7-4
	XPNPEP1	ENST00000488118.6	TSL:1	n.428-48T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75382 AN: 151986 Hom.: 19734 Cov.: 33

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.728

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.600

Gnomad OTH AF: 0.489

GnomAD2 exomes AF: 0.478 AC: 108144 AN: 226460 AF XY: 0.478

Gnomad AFR exome AF: 0.384

Gnomad AMR exome AF: 0.325

Gnomad ASJ exome AF: 0.561

Gnomad EAS exome AF: 0.259

Gnomad FIN exome AF: 0.561

Gnomad NFE exome AF: 0.597

Gnomad OTH exome AF: 0.523

GnomAD4 exome AF: 0.561 AC: 798578 AN: 1422706 Hom.: 232170 Cov.: 23 AF XY: 0.555 AC XY: 392798 AN XY: 708196

African (AFR) AF: 0.384 AC: 12494 AN: 32518

American (AMR) AF: 0.334 AC: 14197 AN: 42568

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 14512 AN: 25674

East Asian (EAS) AF: 0.278 AC: 10793 AN: 38822

South Asian (SAS) AF: 0.306 AC: 25656 AN: 83780

European-Finnish (FIN) AF: 0.569 AC: 29941 AN: 52630

Middle Eastern (MID) AF: 0.451 AC: 2568 AN: 5692

European-Non Finnish (NFE) AF: 0.607 AC: 657129 AN: 1081928

Other (OTH) AF: 0.529 AC: 31288 AN: 59094

GnomAD4 genome AF: 0.496 AC: 75398 AN: 152104 Hom.: 19736 Cov.: 33 AF XY: 0.487 AC XY: 36203 AN XY: 74378

African (AFR) AF: 0.387 AC: 16061 AN: 41492

American (AMR) AF: 0.405 AC: 6199 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.558 AC: 1936 AN: 3470

East Asian (EAS) AF: 0.266 AC: 1374 AN: 5164

South Asian (SAS) AF: 0.291 AC: 1405 AN: 4828

European-Finnish (FIN) AF: 0.551 AC: 5824 AN: 10574

Middle Eastern (MID) AF: 0.486 AC: 142 AN: 292

European-Non Finnish (NFE) AF: 0.600 AC: 40774 AN: 67972

Other (OTH) AF: 0.483 AC: 1019 AN: 2110

Alfa AF: 0.552 Hom.: 20504

Bravo AF: 0.483

Asia WGS AF: 0.251 AC: 877 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.86
DANN	Benign	0.67
PhyloP100		-1.1
Mutation Taster		=100/0	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: rs623980; hg19: chr10-111646147; COSMIC: COSV59167208; COSMIC: COSV59167208;