chr16-88809754-TAAG-T
Position:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PM4_SupportingPP5_Moderate
The NM_000485.3(APRT):c.484_486del(p.Leu162del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 34)
Consequence
APRT
NM_000485.3 inframe_deletion
NM_000485.3 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.56
Genes affected
APRT (HGNC:626): (adenine phosphoribosyltransferase) Adenine phosphoribosyltransferase belongs to the purine/pyrimidine phosphoribosyltransferase family. A conserved feature of this gene is the distribution of CpG dinucleotides. This enzyme catalyzes the formation of AMP and inorganic pyrophosphate from adenine and 5-phosphoribosyl-1-pyrophosphate (PRPP). It also produces adenine as a by-product of the polyamine biosynthesis pathway. A homozygous deficiency in this enzyme causes 2,8-dihydroxyadenine urolithiasis. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PM1
In a chain Adenine phosphoribosyltransferase (size 178) in uniprot entity APT_HUMAN there are 51 pathogenic changes around while only 5 benign (91%) in NM_000485.3
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_000485.3. Strenght limited to Supporting due to length of the change: 1aa.
PP5
Variant 16-88809754-TAAG-T is Pathogenic according to our data. Variant chr16-88809754-TAAG-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1367702.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APRT | NM_000485.3 | c.484_486del | p.Leu162del | inframe_deletion | 5/5 | ENST00000378364.8 | |
APRT | NM_001030018.2 | c.401-51_401-49del | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APRT | ENST00000378364.8 | c.484_486del | p.Leu162del | inframe_deletion | 5/5 | 1 | NM_000485.3 | P1 |
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD3 genomes
Cov.:
34
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome Cov.: 34
GnomAD4 genome
Cov.:
34
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 08, 2022 | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has been observed in individual(s) with APRT deficiency (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This variant, c.484_486del, results in the deletion of 1 amino acid(s) of the APRT protein (p.Leu162del), but otherwise preserves the integrity of the reading frame. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.