chr10-109891797-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_020383.4(XPNPEP1):c.340G>A(p.Ala114Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000417 in 1,607,560 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000041 ( 0 hom. )
Consequence
XPNPEP1
NM_020383.4 missense
NM_020383.4 missense
Scores
1
8
7
Clinical Significance
Conservation
PhyloP100: 7.59
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
XPNPEP1 | NM_020383.4 | c.340G>A | p.Ala114Thr | missense_variant | 5/21 | ENST00000502935.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
XPNPEP1 | ENST00000502935.6 | c.340G>A | p.Ala114Thr | missense_variant | 5/21 | 1 | NM_020383.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000461 AC: 7AN: 151932Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000490 AC: 12AN: 244702Hom.: 0 AF XY: 0.0000377 AC XY: 5AN XY: 132470
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GnomAD4 exome AF: 0.0000412 AC: 60AN: 1455628Hom.: 0 Cov.: 31 AF XY: 0.0000359 AC XY: 26AN XY: 724308
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GnomAD4 genome ? AF: 0.0000461 AC: 7AN: 151932Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2AN XY: 74204
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 05, 2021 | The c.340G>A (p.A114T) alteration is located in exon 5 (coding exon 5) of the XPNPEP1 gene. This alteration results from a G to A substitution at nucleotide position 340, causing the alanine (A) at amino acid position 114 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;D;D
REVEL
Benign
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;T;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at