X-107628475-CG-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The ENST00000643795.2(PRPS1):c.-153delG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000489 in 1,048,004 control chromosomes in the GnomAD database, including 5 homozygotes. There are 151 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00078 ( 0 hom., 26 hem., cov: 23)

Exomes 𝑓: 0.00045 ( 5 hom. 125 hem. )

Consequence

PRPS1
ENST00000643795.2 5_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:4

Conservation

PhyloP100: 1.96

Publications

0 publications found

Variant links:

Genes affected

PRPS1 (HGNC:9462): (phosphoribosyl pyrophosphate synthetase 1) This gene encodes an enzyme that catalyzes the phosphoribosylation of ribose 5-phosphate to 5-phosphoribosyl-1-pyrophosphate, which is necessary for purine metabolism and nucleotide biosynthesis. Defects in this gene are a cause of phosphoribosylpyrophosphate synthetase superactivity, Charcot-Marie-Tooth disease X-linked recessive type 5 and Arts Syndrome. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2011]

PRPS1 Gene-Disease associations (from GenCC):

Arts syndrome
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
Charcot-Marie-Tooth disease X-linked recessive 5
Inheritance: XL Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
hearing loss, X-linked 1
Inheritance: XL Classification: DEFINITIVE Submitted by: G2P
phosphoribosylpyrophosphate synthetase superactivity
Inheritance: XL Classification: DEFINITIVE, STRONG, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P
PRPS1 deficiency disorder
Inheritance: XL Classification: DEFINITIVE Submitted by: Illumina, ClinGen
mild phosphoribosylpyrophosphate synthetase superactivity
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
severe phosphoribosylpyrophosphate synthetase superactivity
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
X-linked intellectual disability-limb spasticity-retinal dystrophy-diabetes insipidus syndrome
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
X-linked nonsyndromic hearing loss
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

PRPS1 links:

ENSG00000294392 (HGNC:):

ENSG00000294392 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP6

Variant X-107628475-CG-C is Benign according to our data. Variant chrX-107628475-CG-C is described in ClinVar as Likely_benign. ClinVar VariationId is 367701.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 26 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000643795.2. 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
	PRPS1	NM_002764.4	MANE Select	c.-153delG		upstream_gene	N/A	NP_002755.1	P60891-1
	PRPS1	NM_001204402.2		c.-357delG		upstream_gene	N/A	NP_001191331.1	B7ZB02

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
PRPS1	ENST00000643795.2	c.-153delG	5_prime_UTR	Exon 1 of 7	ENSP00000496286.1	A0A2R8Y7H4
PRPS1	ENST00000675304.1	n.49delG	non_coding_transcript_exon	Exon 1 of 2
ENSG00000294392	ENST00000723338.1	n.14delC	non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.000795

AC:

AN:

111957

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000520

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000474

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0183

Gnomad SAS

AF:

0.000746

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000670

GnomAD4 exome

AF:

0.000454

AC:

425

AN:

935992

Hom.:

Cov.:

AF XY:

0.000470

AC XY:

125

AN XY:

265746

show subpopulations

African (AFR)

AF:

0.000217

AC:

AN:

23076

American (AMR)

AF:

0.0000295

AC:

AN:

33887

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17660

East Asian (EAS)

AF:

0.00994

AC:

288

AN:

28960

South Asian (SAS)

AF:

0.000285

AC:

AN:

49200

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36755

Middle Eastern (MID)

AF:

0.000397

AC:

AN:

2516

European-Non Finnish (NFE)

AF:

0.0000142

AC:

AN:

703568

Other (OTH)

AF:

0.00263

AC:

106

AN:

40370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000777

AC:

AN:

112012

Hom.:

Cov.:

AF XY:

0.000760

AC XY:

AN XY:

34206

show subpopulations

African (AFR)

AF:

0.000518

AC:

AN:

30867

American (AMR)

AF:

0.000473

AC:

AN:

10563

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2647

East Asian (EAS)

AF:

0.0178

AC:

AN:

3545

South Asian (SAS)

AF:

0.000749

AC:

AN:

2672

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6116

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53190

Other (OTH)

AF:

0.000662

AC:

AN:

1511

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000356

Hom.:

Bravo

AF:

0.000960

Asia WGS

AF:

0.00995

AC:

AN:

2522

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Arts syndrome (1)

Charcot-Marie-Tooth, X-linked (1)

Phosphoribosylpyrophosphate synthetase superactivity (1)

X-linked nonsyndromic hearing loss (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over