16-88809429-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000485.3(APRT):c.*269C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00967 in 591,366 control chromosomes in the GnomAD database, including 229 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.027 (169 hom., cov: 34)
  • Exomes 𝑓: 0.0037 (60 hom.)
• Consequence: APRT NM_000485.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00600

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=0.0018075109).
• BP6: Variant 16-88809429-G-T is Benign according to our data. Variant chr16-88809429-G-T is described in ClinVar as [Benign]. Clinvar id is 1239482.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APRT	NM_000485.3	c.*269C>A		3_prime_UTR_variant	5/5	ENST00000378364.8
APRT	NM_001030018.2			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APRT	ENST00000378364.8	c.*269C>A		3_prime_UTR_variant	5/5	1	NM_000485.3	P1

Frequencies

GnomAD3 genomes AF: 0.0268 AC: 4087 AN: 152246 Hom.: 169 Cov.: 34

Gnomad AFR AF: 0.0935

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00909

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.0215

GnomAD3 exomes AF: 0.00605 AC: 788 AN: 130220 Hom.: 38 AF XY: 0.00436 AC XY: 310 AN XY: 71106

Gnomad AFR exome AF: 0.101

Gnomad AMR exome AF: 0.00559

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000134

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.000364

Gnomad OTH exome AF: 0.00324

GnomAD4 exome AF: 0.00371 AC: 1630 AN: 439002 Hom.: 60 Cov.: 5 AF XY: 0.00279 AC XY: 672 AN XY: 240652

Gnomad4 AFR exome AF: 0.0910

Gnomad4 AMR exome AF: 0.00568

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000246

Gnomad4 FIN exome AF: 0.0000471

Gnomad4 NFE exome AF: 0.000270

Gnomad4 OTH exome AF: 0.00705

GnomAD4 genome AF: 0.0268 AC: 4090 AN: 152364 Hom.: 169 Cov.: 34 AF XY: 0.0260 AC XY: 1941 AN XY: 74524

Gnomad4 AFR AF: 0.0933

Gnomad4 AMR AF: 0.00908

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00103

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000279

Gnomad4 OTH AF: 0.0213

Alfa AF: 0.0157 Hom.: 17

Bravo AF: 0.0307

ExAC AF: 0.00270 AC: 117

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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	-0.34	T
BayesDel_noAF	Benign	-0.19
Cadd	Benign	4.2
Dann	Benign	0.75
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.19	T
MetaRNN	Benign	0.0018	T
MutationTaster	Benign	1.0	N
PROVEAN	Benign	-0.49	N
Sift	Pathogenic	0.0	D
MVP		0.47
GERP RS		-4.5

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs8191499; hg19: chr16-88875837;