16-88809429-G-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.00600

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:

CDT1 (HGNC:24576): (chromatin licensing and DNA replication factor 1) The protein encoded by this gene is involved in the formation of the pre-replication complex that is necessary for DNA replication. The encoded protein can bind geminin, which prevents replication and may function to prevent this protein from initiating replication at inappropriate origins. Phosphorylation of this protein by cyclin A-dependent kinases results in degradation of the protein. [provided by RefSeq, Mar 2011]

CDT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
APRT	NM_000485.3 link	c.*269C>A	3_prime_UTR_variant	Exon 5 of 5	ENST00000378364.8	NP_000476.1	P07741-1
CDT1	NM_030928.4 link	c.*1151G>T	downstream_gene_variant		ENST00000301019.9	NP_112190.2	Q9H211
APRT	NM_001030018.2 link	c.*273C>A	downstream_gene_variant			NP_001025189.1	P07741-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APRT	ENST00000378364 link	c.*269C>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_000485.3	ENSP00000367615.3		P07741-1
CDT1	ENST00000301019.9 link	c.*1151G>T		downstream_gene_variant		1	NM_030928.4	ENSP00000301019.4		Q9H211

Frequencies

GnomAD3 genomes

AF:

0.0268

AC:

4087

AN:

152246

Hom.:

169

Cov.:

show subpopulations

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.:

AF XY:

0.00436

AC XY:

310

AN XY:

71106

show subpopulations

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.:

Cov.:

AF XY:

0.00279

AC XY:

672

AN XY:

240652

show subpopulations

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.:

AF XY:

0.0260

AC XY:

1941

AN XY:

74524

show subpopulations

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.:

Bravo

AF:

0.0307

ExAC

AF:

0.00270

AC:

117

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.19

CADD

Benign

4.2

DANN

Benign

0.75

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.19

MetaRNN

Benign

0.0018

PROVEAN

Benign

-0.49

Sift

Pathogenic

0.0

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

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