X-75274427-C-G

Variant names:

• chrX-75274427-C-G
• rs2082622213
• NM_145052.4:c.173C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_145052.4(UPRT):​c.173C>G​(p.Ser58Cys) 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. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: UPRT NM_145052.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.195

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08009401).
• BP6: Variant X-75274427-C-G is Benign according to our data. Variant chrX-75274427-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2269821.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UPRT	NM_145052.4	c.173C>G	p.Ser58Cys	missense_variant	Exon 1 of 7	ENST00000373383.9	NP_659489.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UPRT	ENST00000373383.9	c.173C>G	p.Ser58Cys	missense_variant	Exon 1 of 7	1	NM_145052.4	ENSP00000362481.4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 04, 2022

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	5.1
DANN	Benign	0.55
DEOGEN2	Benign	0.16	T;.
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.45	T;T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.080	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N;.
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.38	N;N
REVEL	Benign	0.012
Sift	Benign	0.20	T;T
Sift4G	Benign	0.068	T;T
Polyphen		0.0010	B;.
Vest4		0.15
MutPred		0.42		Gain of loop (P = 0.0079);Gain of loop (P = 0.0079);
MVP		0.068
MPC		0.15
ClinPred		0.035	T
GERP RS		1.0
Varity_R		0.066
gMVP		0.51

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

LitVar

Other links and lift over

dbSNP: rs2082622213; hg19: chrX-74494262;