16-88809695-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000485.3(APRT):c.*3A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00994 in 1,613,260 control chromosomes in the GnomAD database, including 1,337 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.053 (694 hom., cov: 34)
  • Exomes 𝑓: 0.0054 (643 hom.)
• Consequence: APRT NM_000485.3 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -6.25

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=-0.93).
• BP6: Variant 16-88809695-T-C is Benign according to our data. Variant chr16-88809695-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 321162.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APRT	NM_000485.3	c.*3A>G		3_prime_UTR_variant	5/5	ENST00000378364.8
APRT	NM_001030018.2	c.*7A>G		3_prime_UTR_variant	5/5

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0533 AC: 8105 AN: 152160 Hom.: 692 Cov.: 34

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0184

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000368

Gnomad OTH AF: 0.0364

GnomAD3 exomes AF: 0.0141 AC: 3536 AN: 250614 Hom.: 294 AF XY: 0.0102 AC XY: 1387 AN XY: 135738

Gnomad AFR exome AF: 0.195

Gnomad AMR exome AF: 0.00897

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000457

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000274

Gnomad OTH exome AF: 0.00506

GnomAD4 exome AF: 0.00541 AC: 7909 AN: 1460982 Hom.: 643 Cov.: 31 AF XY: 0.00447 AC XY: 3252 AN XY: 726802

Gnomad4 AFR exome AF: 0.193

Gnomad4 AMR exome AF: 0.0102

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000383

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000137

Gnomad4 OTH exome AF: 0.0129

GnomAD4 genome AF: 0.0534 AC: 8130 AN: 152278 Hom.: 694 Cov.: 34 AF XY: 0.0521 AC XY: 3883 AN XY: 74460

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.0184

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000828

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000368

Gnomad4 OTH AF: 0.0360

Alfa AF: 0.0157 Hom.: 209

Bravo AF: 0.0615

Asia WGS AF: 0.0140 AC: 47 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000237

ClinVar

Significance: Benign/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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.085
Dann	Benign	0.31
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2070256; hg19: chr16-88876103;