X-75274279-G-C

Position:

• chrX-75274279-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_145052.4(UPRT):​c.25G>C​(p.Asp9His) variant causes a missense change. The variant allele was found at a frequency of 0.00000183 in 1,095,725 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000018 (0 hom. 0 hem.)
• Consequence: UPRT NM_145052.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.61

Genes affected

UPRT (HGNC:28334): (uracil phosphoribosyltransferase homolog) This gene encodes uracil phosphoribosyltransferase, which catalyzes the conversion of uracil and 5-phosphoribosyl-1-R-diphosphate to uridine monophosphate (UMP). This reaction is an important part of nucleotide metabolism, specifically the pyrimidine salvage pathway. The enzyme localizes to the nucleus and cytoplasm. The protein is a potential target for rational design of drugs to treat parasitic infections and cancer. [provided by RefSeq, Nov 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39817822).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UPRT	NM_145052.4	c.25G>C	p.Asp9His	missense_variant	1/7	ENST00000373383.9	NP_659489.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UPRT	ENST00000373383.9	c.25G>C	p.Asp9His	missense_variant	1/7	1	NM_145052.4	ENSP00000362481.4

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000183 AC: 2 AN: 1095725 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 361333

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000238

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 28, 2021

The c.25G>C (p.D9H) alteration is located in exon 1 (coding exon 1) of the UPRT gene. This alteration results from a G to C substitution at nucleotide position 25, causing the aspartic acid (D) at amino acid position 9 to be replaced by a histidine (H). 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	0.14
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Pathogenic	0.34
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T;.
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.82	T;T
M_CAP	Uncertain	0.28	D
MetaRNN	Benign	0.40	T;T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	0.81	L;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.92	N;N
REVEL	Uncertain	0.30
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		1.0	D;.
Vest4		0.55
MutPred		0.20		Loss of solvent accessibility (P = 0.0117);Loss of solvent accessibility (P = 0.0117);
MVP		0.91
MPC		0.70
ClinPred		0.87	D
GERP RS		5.1
Varity_R		0.27
gMVP		0.64

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: chrX-74494114;