16-88809516-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_000485.3(APRT):c.*182A>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 0.00147 in 954,510 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 Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0054 (7 hom., cov: 34)
  • Exomes 𝑓: 0.00072 (6 hom.)
• Consequence: APRT NM_000485.3 3_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: -1.84

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002718091).
• BP6: Variant 16-88809516-T-C is Benign according to our data. Variant chr16-88809516-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 321155.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00541 (825/152366) while in subpopulation AFR AF= 0.0189 (786/41590). 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.*182A>G		3_prime_UTR_variant	5/5	ENST00000378364.8
APRT	NM_001030018.2	c.*186A>G		3_prime_UTR_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APRT	ENST00000378364.8	c.*182A>G		3_prime_UTR_variant	5/5	1	NM_000485.3	P1

Frequencies

GnomAD3 genomes AF: 0.00541 AC: 823 AN: 152248 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: 0.00623

GnomAD3 exomes AF: 0.00163 AC: 236 AN: 144620 Hom.: 0 AF XY: 0.00128 AC XY: 101 AN XY: 78692

Gnomad AFR exome AF: 0.0240

Gnomad AMR exome AF: 0.00212

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000424

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000514

Gnomad OTH exome AF: 0.000698

GnomAD4 exome AF: 0.000722 AC: 579 AN: 802144 Hom.: 6 Cov.: 11 AF XY: 0.000618 AC XY: 258 AN XY: 417400

Gnomad4 AFR exome AF: 0.0214

Gnomad4 AMR exome AF: 0.00180

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000295

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000311

Gnomad4 OTH exome AF: 0.00150

GnomAD4 genome AF: 0.00541 AC: 825 AN: 152366 Hom.: 7 Cov.: 34 AF XY: 0.00535 AC XY: 399 AN XY: 74522

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: 0.00616

Alfa AF: 0.00149 Hom.: 2

Bravo AF: 0.00654

ExAC AF: 0.00112 AC: 124

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Adenine phosphoribosyltransferase deficiency Uncertain:1

Uncertain significance, 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.22
Cadd	Benign	0.89
Dann	Benign	0.91
FATHMM_MKL	Benign	0.0032	N
LIST_S2	Benign	0.19	T
MetaRNN	Benign	0.0027	T
MutationTaster	Benign	1.0	N;N;N
PROVEAN	Benign	-0.070	N
Sift	Uncertain	0.0090	D
MVP		0.46
GERP RS		0.066

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: rs8191498; hg19: chr16-88875924;