rs492943

Variant names:

• chr10-109869272-T-A
• rs492943
• NM_020383.4:c.1774-560A>T

Your query was ambiguous. Multiple possible variants found:

• chr10-109869272-T-A
• chr10-109869272-T-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.752 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.1774-560A>T		intron	N/A	NP_065116.3
	XPNPEP1	NM_001324133.2		c.1774-560A>T		intron	N/A	NP_001311062.1
	XPNPEP1	NM_001324136.1		c.1759-560A>T		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.1774-560A>T		intron	N/A	ENSP00000421566.1
	XPNPEP1	ENST00000322238.12	TSL:1	c.1702-560A>T		intron	N/A	ENSP00000324011.8
	XPNPEP1	ENST00000488118.6	TSL:1	n.3739-560A>T		intron	N/A

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

African (AFR) AF: 0.706 AC: 29310 AN: 41498

American (AMR) AF: 0.551 AC: 8429 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.759 AC: 2625 AN: 3460

East Asian (EAS) AF: 0.605 AC: 3123 AN: 5164

South Asian (SAS) AF: 0.759 AC: 3656 AN: 4818

European-Finnish (FIN) AF: 0.773 AC: 8174 AN: 10574

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.758 AC: 51528 AN: 67982

Other (OTH) AF: 0.692 AC: 1462 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.13
DANN	Benign	0.78
PhyloP100		-2.1
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: rs492943; hg19: chr10-111629030;