rs148080323

Variant names:

• chr10-109865261-C-G
• rs148080323
• NM_020383.4:c.1924G>C

Your query was ambiguous. Multiple possible variants found:

• chr10-109865261-C-G
• chr10-109865261-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020383.4(XPNPEP1):​c.1924G>C​(p.Glu642Gln) variant causes a missense change involving the alteration of a 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E642K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: XPNPEP1 NM_020383.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.33
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38556364).

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.1924G>C	p.Glu642Gln	missense	Exon 21 of 21	NP_065116.3
	XPNPEP1	NM_001324133.2		c.1982G>C	p.Gly661Ala	missense	Exon 22 of 22	NP_001311062.1
	XPNPEP1	NM_001324136.1		c.1909G>C	p.Glu637Gln	missense	Exon 21 of 21	NP_001311065.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XPNPEP1	ENST00000502935.6	TSL:1 MANE Select	c.1924G>C	p.Glu642Gln	missense	Exon 21 of 21	ENSP00000421566.1	Q9NQW7-3
	XPNPEP1	ENST00000322238.12	TSL:1	c.1852G>C	p.Glu618Gln	missense	Exon 20 of 20	ENSP00000324011.8	Q9NQW7-4
	XPNPEP1	ENST00000488118.6	TSL:1	n.3889G>C		non_coding_transcript_exon	Exon 17 of 17

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	23
DANN	Uncertain	0.99
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.90	T
PhyloP100		7.3
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.14
Sift	Benign	0.039	D
Sift4G	Benign	0.33	T
Vest4		0.66
MVP		0.17
MPC		0.69
ClinPred		0.94	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.74
Mutation Taster		=62/38	polymorphism

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: rs148080323; hg19: chr10-111625019;