chrX-107628652-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4BP6_ModerateBP7BS2

The NM_002764.4(PRPS1):c.24C>T(p.Ser8Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,209,764 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000073 ( 0 hom. 5 hem. )

Consequence

PRPS1
NM_002764.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.75

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: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.14).

BP6

Variant X-107628652-C-T is Benign according to our data. Variant chrX-107628652-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1157448.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.75 with no splicing effect.

BS2

High Hemizygotes in GnomAdExome4 at 5 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002764.4. 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
	PRPS1	NM_002764.4	MANE Select	c.24C>T	p.Ser8Ser	synonymous	Exon 1 of 7	NP_002755.1	P60891-1
	PRPS1	NM_001204402.2		c.-181C>T		5_prime_UTR	Exon 1 of 4	NP_001191331.1	B7ZB02

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PRPS1	ENST00000372435.10	TSL:1 MANE Select	c.24C>T	p.Ser8Ser	synonymous	Exon 1 of 7	ENSP00000361512.4	P60891-1
PRPS1	ENST00000643795.2		c.24C>T	p.Ser8Ser	synonymous	Exon 1 of 7	ENSP00000496286.1	A0A2R8Y7H4
PRPS1	ENST00000372418.4	TSL:3	c.24C>T	p.Ser8Ser	synonymous	Exon 1 of 6	ENSP00000361495.2	B1ALA9

Frequencies

GnomAD3 genomes

AF:

0.00000897

AC:

AN:

111524

Hom.:

Cov.:

show subpopulations

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:

0.000377

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000163

AC:

AN:

183488

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000728

AC:

AN:

1098188

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

363546

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26401

American (AMR)

AF:

0.00

AC:

AN:

35206

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19386

East Asian (EAS)

AF:

0.00

AC:

AN:

30203

South Asian (SAS)

AF:

0.000129

AC:

AN:

54147

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40530

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4115

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

842116

Other (OTH)

AF:

0.0000217

AC:

AN:

46084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

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

<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:

0.00000896

AC:

AN:

111576

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33746

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30777

American (AMR)

AF:

0.00

AC:

AN:

10494

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2639

East Asian (EAS)

AF:

0.00

AC:

AN:

3547

South Asian (SAS)

AF:

0.000378

AC:

AN:

2647

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5988

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53059

Other (OTH)

AF:

0.00

AC:

AN:

1523

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Charcot-Marie-Tooth Neuropathy X (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.14

CADD

Benign

(source)

DANN

Benign

0.93

PhyloP100

2.7

PromoterAI

-0.069

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Mutation Taster

=284/16

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over