16-88809520-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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]

ACMG classification

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 GnomAd at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APRT	NM_000485.3	c.*178A>C		3_prime_UTR_variant	5/5	ENST00000378364.8
APRT	NM_001030018.2	c.*182A>C		3_prime_UTR_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APRT	ENST00000378364.8	c.*178A>C		3_prime_UTR_variant	5/5	1	NM_000485.3	P1

Frequencies

GnomAD3 genomes AF: 0.00541 AC: 823 AN: 152162 Hom.: 7 Cov.: 34

Gnomad AFR AF: 0.0189

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00624

GnomAD3 exomes AF: 0.00162 AC: 239 AN: 147086 Hom.: 0 AF XY: 0.00129 AC XY: 103 AN XY: 80096

Gnomad AFR exome AF: 0.0239

Gnomad AMR exome AF: 0.00211

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000421

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000501

Gnomad OTH exome AF: 0.000689

GnomAD4 exome AF: 0.000705 AC: 595 AN: 844478 Hom.: 6 Cov.: 12 AF XY: 0.000613 AC XY: 268 AN XY: 437368

Gnomad4 AFR exome AF: 0.0212

Gnomad4 AMR exome AF: 0.00179

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000291

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000308

Gnomad4 OTH exome AF: 0.00147

GnomAD4 genome AF: 0.00542 AC: 825 AN: 152280 Hom.: 7 Cov.: 34 AF XY: 0.00536 AC XY: 399 AN XY: 74486

Gnomad4 AFR AF: 0.0189

Gnomad4 AMR AF: 0.00131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00617

Alfa AF: 0.000300 Hom.: 176

ExAC AF: 0.00111 AC: 122

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.24
Cadd	Benign	0.42
Dann	Benign	0.36
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.13	T
MetaRNN	Benign	0.0039	T
MutationTaster	Benign	1.0	N;N;N
PROVEAN	Benign	0.18	N
Sift	Benign	0.16	T
MVP		0.42
GERP RS		-4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4695; hg19: chr16-88875928;