16-88809520-T-G
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_000485.3(APRT):c.*178A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00142 in 996,758 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0054 ( 7 hom., cov: 34)
Exomes 𝑓: 0.00070 ( 6 hom. )
Consequence
APRT
NM_000485.3 3_prime_UTR
NM_000485.3 3_prime_UTR
Scores
9
Clinical Significance
Conservation
PhyloP100: -1.77
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 Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.003919691).
BP6
Variant 16-88809520-T-G is Benign according to our data. Variant chr16-88809520-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 321157.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00542 (825/152280) while in subpopulation AFR AF= 0.0189 (786/41530). AF 95% confidence interval is 0.0178. There are 7 homozygotes in gnomad4. There are 399 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 7 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
APRT | NM_000485.3 | c.*178A>C | 3_prime_UTR_variant | 5/5 | ENST00000378364.8 | NP_000476.1 | ||
APRT | NM_001030018.2 | c.*182A>C | 3_prime_UTR_variant | 5/5 | NP_001025189.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
APRT | ENST00000378364 | c.*178A>C | 3_prime_UTR_variant | 5/5 | 1 | NM_000485.3 | ENSP00000367615.3 |
Frequencies
GnomAD3 genomes AF: 0.00541 AC: 823AN: 152162Hom.: 7 Cov.: 34
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GnomAD3 exomes AF: 0.00162 AC: 239AN: 147086Hom.: 0 AF XY: 0.00129 AC XY: 103AN XY: 80096
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GnomAD4 exome AF: 0.000705 AC: 595AN: 844478Hom.: 6 Cov.: 12 AF XY: 0.000613 AC XY: 268AN XY: 437368
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GnomAD4 genome AF: 0.00542 AC: 825AN: 152280Hom.: 7 Cov.: 34 AF XY: 0.00536 AC XY: 399AN XY: 74486
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Adenine phosphoribosyltransferase deficiency Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
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Name
Calibrated prediction
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BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
PROVEAN
Benign
N
Sift
Benign
T
MVP
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at