rs759612541
Positions:
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_ModerateBP6_ModerateBP7BS1
The NM_022098.4(XPNPEP3):c.963C>T(p.Leu321=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000626 in 1,613,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000066 ( 0 hom. )
Consequence
XPNPEP3
NM_022098.4 synonymous
NM_022098.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0730
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 Benign. Variant got -7 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.34).
BP6
?
Variant 22-40909229-C-T is Benign according to our data. Variant chr22-40909229-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 414175.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.073 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.0000657 (96/1461672) while in subpopulation EAS AF= 0.00232 (92/39696). AF 95% confidence interval is 0.00193. There are 0 homozygotes in gnomad4_exome. There are 45 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
XPNPEP3 | NM_022098.4 | c.963C>T | p.Leu321= | synonymous_variant | 6/10 | ENST00000357137.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
XPNPEP3 | ENST00000357137.9 | c.963C>T | p.Leu321= | synonymous_variant | 6/10 | 1 | NM_022098.4 | P1 | |
XPNPEP3 | ENST00000428799.1 | c.*845C>T | 3_prime_UTR_variant, NMD_transcript_variant | 7/11 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152216Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000915 AC: 23AN: 251482Hom.: 0 AF XY: 0.0000956 AC XY: 13AN XY: 135918
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GnomAD4 exome AF: 0.0000657 AC: 96AN: 1461672Hom.: 0 Cov.: 31 AF XY: 0.0000619 AC XY: 45AN XY: 727154
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GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152216Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74360
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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 | Jan 15, 2024 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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