Variant 16-88809516-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

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

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -1.84

Variant links:

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]

APRT links:

APRT (HGNC:):

APRT links:

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ACMG classification

Classification made for transcript

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: {Likely_benign=1, Uncertain_significance=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 GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APRT	NM_000485.3 linkuse as main transcript	c.*182A>G		3_prime_UTR_variant	5/5	ENST00000378364.8	NP_000476.1	P07741-1
APRT	NM_001030018.2 linkuse as main transcript	c.*186A>G		3_prime_UTR_variant	5/5		NP_001025189.1	P07741-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APRT	ENST00000378364 linkuse as main transcript	c.*182A>G		3_prime_UTR_variant	5/5	1	NM_000485.3	ENSP00000367615.3		P07741-1

Frequencies

GnomAD3 genomes

AF:

0.00541

AC:

823

AN:

152248

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00128

AC XY:

101

AN XY:

78692

show subpopulations

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.:

Cov.:

AF XY:

0.000618

AC XY:

258

AN XY:

417400

show subpopulations

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.:

Cov.:

AF XY:

0.00535

AC XY:

399

AN XY:

74522

show subpopulations

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.:

Bravo

AF:

0.00654

ExAC

AF:

0.00112

AC:

124

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

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

BayesDel_noAF

Benign

-0.22

CADD

Benign

0.89

DANN

Benign

0.91

FATHMM_MKL

Benign

0.0032

LIST_S2

Benign

0.19

MetaRNN

Benign

0.0027

PROVEAN

Benign

-0.070

Sift

Uncertain

0.0090

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over