16-88809727-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1 PM2 BP4

The NM_000485.3(APRT):c.514C>G(p.Pro172Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: APRT NM_000485.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.57

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM1: In a chain Adenine phosphoribosyltransferase (size 178) in uniprot entity APT_HUMAN there are 51 pathogenic changes around while only 5 benign (91%) in NM_000485.3
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28599304).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APRT	NM_000485.3	c.514C>G	p.Pro172Ala	missense_variant	5/5	ENST00000378364.8
APRT	NM_001030018.2	c.401-21C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APRT	ENST00000378364.8	c.514C>G	p.Pro172Ala	missense_variant	5/5	1	NM_000485.3	P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 05, 2024

The c.514C>G (p.P172A) alteration is located in exon 5 (coding exon 5) of the APRT gene. This alteration results from a C to G substitution at nucleotide position 514, causing the proline (P) at amino acid position 172 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
Cadd	Benign	22
Dann	Uncertain	0.99
DEOGEN2	Uncertain	0.65	D;T
Eigen	Benign	-0.026
Eigen_PC	Benign	0.049
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.29	T;T
MetaSVM	Uncertain	0.54	D
MutationAssessor	Uncertain	2.1	M;.
MutationTaster	Benign	0.99	D;D;D
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-5.1	D;D
REVEL	Uncertain	0.37
Sift	Benign	0.036	D;D
Sift4G	Benign	0.090	T;T
Polyphen		0.30	B;.
Vest4		0.15
MutPred		0.42		Loss of ubiquitination at K167 (P = 0.1166);.;
MVP		0.89
MPC		0.14
ClinPred		0.83	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.44
gMVP		0.42

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-88876135;