rs104894507

Variant names:

• chr16-88810450-C-G
• NM_000485.3:c.294G>C

Your query was ambiguous. Multiple possible variants found:

• chr16-88810450-C-G
• chr16-88810450-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_000485.3(APRT):​c.294G>C​(p.Trp98Cys) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: APRT NM_000485.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.85

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 2 ACMG points.

• PM1: In a chain Adenine phosphoribosyltransferase (size 178) in uniprot entity APT_HUMAN there are 22 pathogenic changes around while only 1 benign (96%) in NM_000485.3
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.091836154).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APRT	NM_000485.3	c.294G>C	p.Trp98Cys	missense_variant	Exon 3 of 5	ENST00000378364.8	NP_000476.1
APRT	NM_001030018.2	c.294G>C	p.Trp98Cys	missense_variant	Exon 3 of 5		NP_001025189.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APRT	ENST00000378364.8	c.294G>C	p.Trp98Cys	missense_variant	Exon 3 of 5	1	NM_000485.3	ENSP00000367615.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.083	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	0.0040
DANN	Benign	0.71
DEOGEN2	Uncertain	0.42	T;.;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.11	N
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.092	T;T;T
MetaSVM	Uncertain	-0.011	T
MutationAssessor	Benign	-1.1	N;.;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.59	N;N;N
REVEL	Uncertain	0.43
Sift	Benign	0.031	D;T;D
Sift4G	Benign	0.083	T;.;T
Polyphen		0.0	B;.;.
Vest4		0.28
MutPred		0.46		Gain of catalytic residue at S100 (P = 0.0541);Gain of catalytic residue at S100 (P = 0.0541);Gain of catalytic residue at S100 (P = 0.0541);
MVP		0.57
MPC		0.22
ClinPred		0.078	T
GERP RS		-9.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.20
gMVP		0.66

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-88876858;