chr16-88809695-T-C

Variant names:

• chr16-88809695-T-C
• rs2070256
• NM_000485.3:c.*3A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000485.3(APRT):​c.*3A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00994 in 1,613,260 control chromosomes in the GnomAD database, including 1,337 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.053 (694 hom., cov: 34)
  • Exomes 𝑓: 0.0054 (643 hom.)
• Consequence: APRT NM_000485.3 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -6.25
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 16-88809695-T-C is Benign according to our data. Variant chr16-88809695-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 321162.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.183 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APRT	NM_000485.3	MANE Select	c.*3A>G		3_prime_UTR	Exon 5 of 5	NP_000476.1	P07741-1
	APRT	NM_001030018.2		c.*7A>G		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.*3A>G		3_prime_UTR	Exon 5 of 5	ENSP00000367615.3	P07741-1
	APRT	ENST00000912471.1		c.*3A>G		3_prime_UTR	Exon 5 of 5	ENSP00000582530.1
	APRT	ENST00000880214.1		c.*3A>G		3_prime_UTR	Exon 5 of 5	ENSP00000550273.1

Frequencies

GnomAD3 genomes AF: 0.0533 AC: 8105 AN: 152160 Hom.: 692 Cov.: 34

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0184

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000368

Gnomad OTH AF: 0.0364

GnomAD2 exomes AF: 0.0141 AC: 3536 AN: 250614 AF XY: 0.0102

Gnomad AFR exome AF: 0.195

Gnomad AMR exome AF: 0.00897

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000274

Gnomad OTH exome AF: 0.00506

GnomAD4 exome AF: 0.00541 AC: 7909 AN: 1460982 Hom.: 643 Cov.: 31 AF XY: 0.00447 AC XY: 3252 AN XY: 726802

African (AFR) AF: 0.193 AC: 6451 AN: 33476

American (AMR) AF: 0.0102 AC: 458 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000383 AC: 33 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52582

Middle Eastern (MID) AF: 0.00676 AC: 39 AN: 5768

European-Non Finnish (NFE) AF: 0.000137 AC: 152 AN: 1111964

Other (OTH) AF: 0.0129 AC: 776 AN: 60382

GnomAD4 genome AF: 0.0534 AC: 8130 AN: 152278 Hom.: 694 Cov.: 34 AF XY: 0.0521 AC XY: 3883 AN XY: 74460

African (AFR) AF: 0.186 AC: 7743 AN: 41536

American (AMR) AF: 0.0184 AC: 281 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000368 AC: 25 AN: 68018

Other (OTH) AF: 0.0360 AC: 76 AN: 2112

Alfa AF: 0.0210 Hom.: 386

Bravo AF: 0.0615

Asia WGS AF: 0.0140 AC: 47 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Adenine phosphoribosyltransferase deficiency (1)
-	-	1	Morquio syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.085
DANN	Benign	0.31
PhyloP100		-6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2070256; hg19: chr16-88876103;