chr22-40922399-C-T
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7
The NM_022098.4(XPNPEP3):c.1122C>T(p.Leu374=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,461,644 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.000017 ( 1 hom. )
Consequence
XPNPEP3
NM_022098.4 synonymous
NM_022098.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.272
Genes affected
XPNPEP3 (HGNC:28052): (X-prolyl aminopeptidase 3) The protein encoded by this gene belongs to the family of X-pro-aminopeptidases that utilize a metal cofactor, and remove the N-terminal amino acid from peptides with a proline residue in the penultimate position. This protein has been shown to localize to the mitochondria of renal cells, and have a role in ciliary function. Mutations in this gene are associated with nephronophthisis-like nephropathy-1. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene, however, expression of some of these isoforms in vivo is not known.[provided by RefSeq, Mar 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
?
Variant 22-40922399-C-T is Benign according to our data. Variant chr22-40922399-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 241419.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.272 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
XPNPEP3 | NM_022098.4 | c.1122C>T | p.Leu374= | synonymous_variant | 8/10 | ENST00000357137.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
XPNPEP3 | ENST00000357137.9 | c.1122C>T | p.Leu374= | synonymous_variant | 8/10 | 1 | NM_022098.4 | P1 | |
XPNPEP3 | ENST00000428799.1 | c.*1004C>T | 3_prime_UTR_variant, NMD_transcript_variant | 9/11 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251132Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135736
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GnomAD4 exome AF: 0.0000171 AC: 25AN: 1461644Hom.: 1 Cov.: 31 AF XY: 0.0000248 AC XY: 18AN XY: 727130
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GnomAD4 genome ? Cov.: 31
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Nephronophthisis-like nephropathy 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 24, 2015 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at