10-109869272-T-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020383.4(XPNPEP1):​c.1774-560A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: XPNPEP1 NM_020383.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

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>C		intron	N/A	NP_065116.3
	XPNPEP1	NM_001324133.2		c.1774-560A>C		intron	N/A	NP_001311062.1
	XPNPEP1	NM_001324136.1		c.1759-560A>C		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>C		intron	N/A	ENSP00000421566.1
	XPNPEP1	ENST00000322238.12	TSL:1	c.1702-560A>C		intron	N/A	ENSP00000324011.8
	XPNPEP1	ENST00000488118.6	TSL:1	n.3739-560A>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.12
DANN	Benign	0.74
PhyloP100		-2.1

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;