rs7075964

Positions:

• chr10-109871507-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020383.4(XPNPEP1):​c.1522+285G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,186 control chromosomes in the GnomAD database, including 2,184 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 0.15 (2184 hom., cov: 32)
• Consequence: XPNPEP1 NM_020383.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.321

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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XPNPEP1	NM_020383.4	c.1522+285G>T		intron_variant		ENST00000502935.6	NP_065116.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XPNPEP1	ENST00000502935.6	c.1522+285G>T		intron_variant		1	NM_020383.4	ENSP00000421566	P1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22957 AN: 152068 Hom.: 2185 Cov.: 32

Gnomad AFR AF: 0.0950

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.147

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.151 AC: 22963 AN: 152186 Hom.: 2184 Cov.: 32 AF XY: 0.159 AC XY: 11842 AN XY: 74382

Gnomad4 AFR AF: 0.0948

Gnomad4 AMR AF: 0.112

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.340

Gnomad4 SAS AF: 0.391

Gnomad4 FIN AF: 0.212

Gnomad4 NFE AF: 0.152

Gnomad4 OTH AF: 0.149

Alfa AF: 0.146 Hom.: 334

Bravo AF: 0.135

Asia WGS AF: 0.355 AC: 1236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.4
DANN	Benign	0.43

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: rs7075964; hg19: chr10-111631265;