rs2273740

chr10-109877877-A-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_020383.4(XPNPEP1):c.1242-10T>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 1,613,996 control chromosomes in the GnomAD database, including 31,642 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 0.20 (3644 hom., cov: 33)
  • Exomes 𝑓: 0.18 (27998 hom.)
• Consequence: XPNPEP1 NM_020383.4 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.03768
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.47

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XPNPEP1	NM_020383.4	c.1242-10T>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000502935.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XPNPEP1	ENST00000502935.6	c.1242-10T>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_020383.4	P1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30889 AN: 152060 Hom.: 3637 Cov.: 33

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.179

GnomAD3 exomes AF: 0.216 AC: 54362 AN: 251432 Hom.: 7637 AF XY: 0.228 AC XY: 31024 AN XY: 135890

Gnomad AFR exome AF: 0.233

Gnomad AMR exome AF: 0.0827

Gnomad ASJ exome AF: 0.182

Gnomad EAS exome AF: 0.366

Gnomad SAS exome AF: 0.433

Gnomad FIN exome AF: 0.296

Gnomad NFE exome AF: 0.161

Gnomad OTH exome AF: 0.188

GnomAD4 exome AF: 0.179 AC: 261196 AN: 1461816 Hom.: 27998 Cov.: 33 AF XY: 0.186 AC XY: 135507 AN XY: 727210

Gnomad4 AFR exome AF: 0.236

Gnomad4 AMR exome AF: 0.0882

Gnomad4 ASJ exome AF: 0.181

Gnomad4 EAS exome AF: 0.320

Gnomad4 SAS exome AF: 0.425

Gnomad4 FIN exome AF: 0.283

Gnomad4 NFE exome AF: 0.150

Gnomad4 OTH exome AF: 0.196

GnomAD4 genome AF: 0.203 AC: 30919 AN: 152180 Hom.: 3644 Cov.: 33 AF XY: 0.214 AC XY: 15896 AN XY: 74392

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.352

Gnomad4 SAS AF: 0.429

Gnomad4 FIN AF: 0.308

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.181

Alfa AF: 0.179 Hom.: 848

Bravo AF: 0.185

Asia WGS AF: 0.388 AC: 1349 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
Cadd	Benign	19
Dann	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.038
dbscSNV1_RF	Benign	0.28
SpliceAI score (max)		0.020		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: rs2273740; hg19: chr10-111637635; COSMIC: COSV59167195; COSMIC: COSV59167195;