rs8191499

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

Meier-Gorlin syndrome 4
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen
Meier-Gorlin syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CDT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000485.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
APRT	NM_000485.3	MANE Select	c.*269C>A	3_prime_UTR	Exon 5 of 5	NP_000476.1	P07741-1
CDT1	NM_030928.4	MANE Select	c.*1151G>T	downstream_gene	N/A	NP_112190.2	Q9H211
APRT	NM_001030018.2		c.*273C>A	downstream_gene	N/A	NP_001025189.1	P07741-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
APRT	ENST00000378364.8	TSL:1 MANE Select	c.*269C>A		3_prime_UTR	Exon 5 of 5	ENSP00000367615.3	P07741-1
APRT	ENST00000567713.5	TSL:5	c.428C>A	p.Pro143His	missense	Exon 4 of 4	ENSP00000455749.1	H3BQF1
CDT1	ENST00000301019.9	TSL:1 MANE Select	c.*1151G>T		downstream_gene	N/A	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

GnomAD2 exomes

AF:

0.00605

AC:

788

AN:

130220

AF XY:

0.00436

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 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

African (AFR)

AF:

0.0910

AC:

1195

AN:

13134

American (AMR)

AF:

0.00568

AC:

175

AN:

30804

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16404

East Asian (EAS)

AF:

0.00

AC:

AN:

21016

South Asian (SAS)

AF:

0.000246

AC:

AN:

60980

European-Finnish (FIN)

AF:

0.0000471

AC:

AN:

21238

Middle Eastern (MID)

AF:

0.00308

AC:

AN:

3568

European-Non Finnish (NFE)

AF:

0.000270

AC:

AN:

248306

Other (OTH)

AF:

0.00705

AC:

166

AN:

23552

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

184

276

368

460

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0268

AC:

4090

AN:

152364

Hom.:

169

Cov.:

AF XY:

0.0260

AC XY:

1941

AN XY:

74524

show subpopulations

African (AFR)

AF:

0.0933

AC:

3880

AN:

41572

American (AMR)

AF:

0.00908

AC:

139

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00103

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000279

AC:

AN:

68038

Other (OTH)

AF:

0.0213

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

194

388

582

776

970

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

192

240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0173

Hom.:

Bravo

AF:

0.0307

ExAC

AF:

0.00270

AC:

117

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.19

CADD

Benign

4.2

(source)

DANN

Benign

0.75

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.19

MetaRNN

Benign

0.0018

PhyloP100

-0.0060

PROVEAN

Benign

-0.49

Sift

Pathogenic

0.0

MVP

0.47

GERP RS

-4.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over