16-88809520-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.*178A>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 0.0958 in 996,258 control chromosomes in the GnomAD database, including 9,038 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (4166 hom., cov: 34)
  • Exomes 𝑓: 0.082 (4872 hom.)
• Consequence: APRT NM_000485.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.8258562E-4).
• BP6: Variant 16-88809520-T-C is Benign according to our data. Variant chr16-88809520-T-C is described in ClinVar as [Benign]. Clinvar id is 321156.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25933 AN: 152134 Hom.: 4155 Cov.: 34

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.0250

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.0407

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.0688

Gnomad OTH AF: 0.149

GnomAD3 exomes AF: 0.0981 AC: 14435 AN: 147086 Hom.: 1321 AF XY: 0.0975 AC XY: 7806 AN XY: 80096

Gnomad AFR exome AF: 0.444

Gnomad AMR exome AF: 0.0607

Gnomad ASJ exome AF: 0.175

Gnomad EAS exome AF: 0.0254

Gnomad SAS exome AF: 0.124

Gnomad FIN exome AF: 0.0400

Gnomad NFE exome AF: 0.0708

Gnomad OTH exome AF: 0.0935

GnomAD4 exome AF: 0.0823 AC: 69453 AN: 844006 Hom.: 4872 Cov.: 12 AF XY: 0.0833 AC XY: 36401 AN XY: 437136

Gnomad4 AFR exome AF: 0.428

Gnomad4 AMR exome AF: 0.0692

Gnomad4 ASJ exome AF: 0.176

Gnomad4 EAS exome AF: 0.0180

Gnomad4 SAS exome AF: 0.125

Gnomad4 FIN exome AF: 0.0377

Gnomad4 NFE exome AF: 0.0664

Gnomad4 OTH exome AF: 0.104

GnomAD4 genome AF: 0.171 AC: 25986 AN: 152252 Hom.: 4166 Cov.: 34 AF XY: 0.167 AC XY: 12461 AN XY: 74468

Gnomad4 AFR AF: 0.425

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.0249

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.0407

Gnomad4 NFE AF: 0.0688

Gnomad4 OTH AF: 0.148

Alfa AF: 0.0694 Hom.: 176

Bravo AF: 0.187

TwinsUK AF: 0.0620 AC: 230

ALSPAC AF: 0.0669 AC: 258

ExAC AF: 0.0753 AC: 8297

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Adenine phosphoribosyltransferase deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Morquio syndrome Benign:1

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_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.25
Cadd	Benign	0.49
Dann	Benign	0.63
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.15	T
MetaRNN	Benign	0.00028	T
MutationTaster	Benign	1.0	P;P;P
PROVEAN	Benign	0.38	N
Sift	Benign	0.32	T
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;