NM_000485.3:c.542G>C

Variant names:

• chr16-88809699-C-G
• rs387906584
• NM_000485.3:c.542G>C

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2 PM4 PP5

The NM_000485.3(APRT):​c.542G>C​(p.Ter181Serext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,206 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 34)
• Consequence: APRT NM_000485.3 stop_lost
• Clinical Significance: Pathogenic no assertion criteria provided P:2
• Conservation: PhyloP100: 1.14
• Publications: 2 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in NM_000485.3 Downstream stopcodon found after 42 codons.
• PP5: Variant 16-88809699-C-G is Pathogenic according to our data. Variant chr16-88809699-C-G is described in ClinVar as Pathogenic. ClinVar VariationId is 18302.Status of the report is no_assertion_criteria_provided, 0 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.542G>C	p.Ter181Serext*?	stop_lost	Exon 5 of 5	NP_000476.1	P07741-1
	APRT	NM_001030018.2		c.*3G>C		3_prime_UTR	Exon 5 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.542G>C	p.Ter181Serext*?	stop_lost	Exon 5 of 5	ENSP00000367615.3	P07741-1
	APRT	ENST00000912471.1		c.788G>C	p.Ter263Serext*?	stop_lost	Exon 5 of 5	ENSP00000582530.1
	APRT	ENST00000880214.1		c.635G>C	p.Ter212Serext*?	stop_lost	Exon 5 of 5	ENSP00000550273.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152206 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152206 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 74342

African (AFR) AF: 0.00 AC: 0 AN: 41444

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
2	-	-	Adenine phosphoribosyltransferase deficiency (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	15
DANN	Benign	0.68
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.96	D
PhyloP100		1.1
Vest4		0.14
GERP RS		3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=8/192	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs387906584; hg19: chr16-88876107;