rs144630001

Variant names:

• chrX-75274469-C-G
• rs144630001
• NM_145052.4:c.215C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-75274469-C-G
• chrX-75274469-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145052.4(UPRT):​c.215C>G​(p.Ser72Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000331 in 1,209,717 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S72F) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.0000018 (0 hom. 1 hem.)
• Consequence: UPRT NM_145052.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.102984846).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145052.4. 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
	UPRT	NM_145052.4	MANE Select	c.215C>G	p.Ser72Cys	missense	Exon 1 of 7	NP_659489.1	Q96BW1-1
	UPRT	NM_001307944.1		c.215C>G	p.Ser72Cys	missense	Exon 1 of 7	NP_001294873.1	A0A0A0MRR5
	UPRT	NM_001363821.1		c.-22-19003C>G		intron	N/A	NP_001350750.1	E9PSD7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UPRT	ENST00000373383.9	TSL:1 MANE Select	c.215C>G	p.Ser72Cys	missense	Exon 1 of 7	ENSP00000362481.4	Q96BW1-1
	UPRT	ENST00000462237.5	TSL:1	n.215C>G		non_coding_transcript_exon	Exon 1 of 8	ENSP00000433987.1	Q96BW1-2
	UPRT	ENST00000531704.5	TSL:1	n.385C>G		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes AF: 0.0000179 AC: 2 AN: 111840 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000376

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1097877 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 1 AN XY: 363283

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26401

American (AMR) AF: 0.00 AC: 0 AN: 35166

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19376

East Asian (EAS) AF: 0.00 AC: 0 AN: 30191

South Asian (SAS) AF: 0.00 AC: 0 AN: 54089

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40436

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4132

European-Non Finnish (NFE) AF: 0.00000238 AC: 2 AN: 842030

Other (OTH) AF: 0.00 AC: 0 AN: 46056

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000179 AC: 2 AN: 111840 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34000

African (AFR) AF: 0.00 AC: 0 AN: 30753

American (AMR) AF: 0.00 AC: 0 AN: 10574

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2650

East Asian (EAS) AF: 0.00 AC: 0 AN: 3521

South Asian (SAS) AF: 0.00 AC: 0 AN: 2653

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6098

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.0000376 AC: 2 AN: 53165

Other (OTH) AF: 0.00 AC: 0 AN: 1503

Alfa AF: 0.0000105 Hom.: 46

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	13
DANN	Benign	0.96
DEOGEN2	Benign	0.17	T
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.090
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.15
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.042	D
Polyphen		0.22	B
Vest4		0.23
MutPred		0.32		Loss of phosphorylation at S72 (P = 0.024)
MVP		0.043
MPC		0.27
ClinPred		0.57	D
GERP RS		-2.2
PromoterAI		0.024	Neutral
Varity_R		0.070
gMVP		0.28
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs144630001; hg19: chrX-74494304;