rs623980

chr10-109886389-A-Gchr10-109886389-A-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XPNPEP1	NM_020383.4	c.653-48T>C		intron_variant		ENST00000502935.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XPNPEP1	ENST00000502935.6	c.653-48T>C		intron_variant		1	NM_020383.4	P1

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

GnomAD3 exomes AF: 0.478 AC: 108144 AN: 226460 Hom.: 27986 AF XY: 0.478 AC XY: 58327 AN XY: 121928

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 SAS exome AF: 0.303

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

Gnomad4 AFR exome AF: 0.384

Gnomad4 AMR exome AF: 0.334

Gnomad4 ASJ exome AF: 0.565

Gnomad4 EAS exome AF: 0.278

Gnomad4 SAS exome AF: 0.306

Gnomad4 FIN exome AF: 0.569

Gnomad4 NFE exome AF: 0.607

Gnomad4 OTH exome AF: 0.529

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

Gnomad4 AFR AF: 0.387

Gnomad4 AMR AF: 0.405

Gnomad4 ASJ AF: 0.558

Gnomad4 EAS AF: 0.266

Gnomad4 SAS AF: 0.291

Gnomad4 FIN AF: 0.551

Gnomad4 NFE AF: 0.600

Gnomad4 OTH AF: 0.483

Alfa AF: 0.551 Hom.: 17122

Bravo AF: 0.483

Asia WGS AF: 0.251 AC: 877 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	0.86
Dann	Benign	0.67

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: rs623980; hg19: chr10-111646147; COSMIC: COSV59167208; COSMIC: COSV59167208;