Variant 16-88809615-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting

The NM_000485.3(APRT):c.*83G>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 0.00108 in 1,591,740 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00061 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0011 ( 1 hom. )

Consequence

APRT
NM_000485.3 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.90

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000611 (93/152256) while in subpopulation NFE AF= 0.000985 (67/68046). AF 95% confidence interval is 0.000795. There are 0 homozygotes in gnomad4. There are 35 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APRT	NM_000485.3 linkuse as main transcript	c.*83G>A		3_prime_UTR_variant	5/5	ENST00000378364.8	NP_000476.1	P07741-1
APRT	NM_001030018.2 linkuse as main transcript	c.*87G>A		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.*83G>A		3_prime_UTR_variant	5/5	1	NM_000485.3	ENSP00000367615.3		P07741-1

Frequencies

GnomAD3 genomes

AF:

0.000611

AC:

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000985

Gnomad OTH

AF:

0.00143

GnomAD4 exome

AF:

0.00113

AC:

1624

AN:

1439484

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

790

AN XY:

716886

show subpopulations

Gnomad4 AFR exome

AF:

0.000304

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.0000770

Gnomad4 EAS exome

AF:

0.0000506

Gnomad4 SAS exome

AF:

0.000105

Gnomad4 FIN exome

AF:

0.0000196

Gnomad4 NFE exome

AF:

0.00142

Gnomad4 OTH exome

AF:

0.000805

GnomAD4 genome

AF:

0.000611

AC:

AN:

152256

Hom.:

Cov.:

AF XY:

0.000470

AC XY:

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.000555

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000985

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.000416

Hom.:

Bravo

AF:

0.000567

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.19

DANN

Benign

0.55

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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