rs492943

Positions:

• chr10-109869272-T-A

Variant summary

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

The NM_020383.4(XPNPEP1):​c.1774-560A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 152,100 control chromosomes in the GnomAD database, including 39,587 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 0.72 (39587 hom., cov: 32)
• Consequence: XPNPEP1 NM_020383.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06

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]

XPNPEP1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XPNPEP1	NM_020383.4	c.1774-560A>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.1774-560A>T		intron_variant		1	NM_020383.4	ENSP00000421566.1

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109250 AN: 151982 Hom.: 39579 Cov.: 32

Gnomad AFR AF: 0.707

Gnomad AMI AF: 0.850

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.759

Gnomad EAS AF: 0.605

Gnomad SAS AF: 0.759

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.758

Gnomad OTH AF: 0.696

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

GnomAD4 genome AF: 0.719 AC: 109294 AN: 152100 Hom.: 39587 Cov.: 32 AF XY: 0.717 AC XY: 53293 AN XY: 74344

Gnomad4 AFR AF: 0.706

Gnomad4 AMR AF: 0.551

Gnomad4 ASJ AF: 0.759

Gnomad4 EAS AF: 0.605

Gnomad4 SAS AF: 0.759

Gnomad4 FIN AF: 0.773

Gnomad4 NFE AF: 0.758

Gnomad4 OTH AF: 0.692

Alfa AF: 0.744 Hom.: 5290

Bravo AF: 0.697

Asia WGS AF: 0.647 AC: 2254 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.13
DANN	Benign	0.78

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: rs492943; hg19: chr10-111629030;