16-88809651-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000485.3(APRT):c.*47T>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 0.0131 in 1,612,214 control chromosomes in the GnomAD database, including 306 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (45 hom., cov: 34)
  • Exomes 𝑓: 0.013 (261 hom.)
• Consequence: APRT NM_000485.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.53

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 16-88809651-A-G is Benign according to our data. Variant chr16-88809651-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 321161.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0191 (2910/152262) while in subpopulation AFR AF= 0.0422 (1752/41538). AF 95% confidence interval is 0.0405. There are 45 homozygotes in gnomad4. There are 1392 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 44 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APRT	NM_000485.3	c.*47T>C		3_prime_UTR_variant	5/5	ENST00000378364.8
APRT	NM_001030018.2	c.*51T>C		3_prime_UTR_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APRT	ENST00000378364.8	c.*47T>C		3_prime_UTR_variant	5/5	1	NM_000485.3	P1

Frequencies

GnomAD3 genomes AF: 0.0190 AC: 2898 AN: 152144 Hom.: 44 Cov.: 34

Gnomad AFR AF: 0.0420

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0118

Gnomad ASJ AF: 0.0317

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0364

Gnomad FIN AF: 0.00226

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00889

Gnomad OTH AF: 0.0172

GnomAD3 exomes AF: 0.0149 AC: 3728 AN: 249990 Hom.: 67 AF XY: 0.0165 AC XY: 2231 AN XY: 135502

Gnomad AFR exome AF: 0.0421

Gnomad AMR exome AF: 0.00486

Gnomad ASJ exome AF: 0.0270

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0452

Gnomad FIN exome AF: 0.00243

Gnomad NFE exome AF: 0.00954

Gnomad OTH exome AF: 0.0164

GnomAD4 exome AF: 0.0125 AC: 18255 AN: 1459952 Hom.: 261 Cov.: 31 AF XY: 0.0135 AC XY: 9821 AN XY: 726268

Gnomad4 AFR exome AF: 0.0437

Gnomad4 AMR exome AF: 0.00597

Gnomad4 ASJ exome AF: 0.0284

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0434

Gnomad4 FIN exome AF: 0.00224

Gnomad4 NFE exome AF: 0.00975

Gnomad4 OTH exome AF: 0.0157

GnomAD4 genome AF: 0.0191 AC: 2910 AN: 152262 Hom.: 45 Cov.: 34 AF XY: 0.0187 AC XY: 1392 AN XY: 74472

Gnomad4 AFR AF: 0.0422

Gnomad4 AMR AF: 0.0118

Gnomad4 ASJ AF: 0.0317

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0369

Gnomad4 FIN AF: 0.00226

Gnomad4 NFE AF: 0.00890

Gnomad4 OTH AF: 0.0170

Alfa AF: 0.0121 Hom.: 18

Bravo AF: 0.0197

Asia WGS AF: 0.0150 AC: 53 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Adenine phosphoribosyltransferase deficiency Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Morquio syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 19, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.67
Dann	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs8191497; hg19: chr16-88876059;