16-88810451-C-T

Variant names:

• chr16-88810451-C-T
• rs281860264
• NM_000485.3:c.293G>A
• APRT p.Trp98*

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_000485.3(APRT):​c.293G>A​(p.Trp98*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: APRT NM_000485.3 stop_gained
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 1.31
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• adenine phosphoribosyltransferase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Pathogenic. The variant received 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 16-88810451-C-T is Pathogenic according to our data. Variant chr16-88810451-C-T is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 3581350.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APRT	NM_000485.3	MANE Select	c.293G>A	p.Trp98*	stop_gained	Exon 3 of 5	NP_000476.1	P07741-1
	APRT	NM_001030018.2		c.293G>A	p.Trp98*	stop_gained	Exon 3 of 5	NP_001025189.1	P07741-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APRT	ENST00000378364.8	TSL:1 MANE Select	c.293G>A	p.Trp98*	stop_gained	Exon 3 of 5	ENSP00000367615.3	P07741-1
	APRT	ENST00000912471.1		c.539G>A	p.Trp180*	stop_gained	Exon 3 of 5	ENSP00000582530.1
	APRT	ENST00000880214.1		c.386G>A	p.Trp129*	stop_gained	Exon 3 of 5	ENSP00000550273.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Adenine phosphoribosyltransferase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.63	D
BayesDel_noAF	Pathogenic	0.28
CADD	Pathogenic	36
DANN	Benign	0.96
Eigen	Uncertain	0.24
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.39	N
PhyloP100		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs281860264;

hg19: chr16-88876859;