X-107628475-CG-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The ENST00000643795.2(PRPS1):c.-153del 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
• Clinical Significance: Likely benign criteria provided, single submitter B:4
• Conservation: PhyloP100: 1.96

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]

ACMG classification

Verdict is Likely_benign. Variant got -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 id is 367701.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd at 26 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRPS1	NM_002764.4			upstream_gene_variant		ENST00000372435.10
PRPS1	NM_001204402.2			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRPS1	ENST00000372435.10			upstream_gene_variant		1	NM_002764.4	P1

Frequencies

GnomAD3 genomes AF: 0.000795 AC: 89 AN: 111957 Hom.: 0 Cov.: 23 AF XY: 0.000762 AC XY: 26 AN XY: 34141

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.: 5 Cov.: 15 AF XY: 0.000470 AC XY: 125 AN XY: 265746

Gnomad4 AFR exome AF: 0.000217

Gnomad4 AMR exome AF: 0.0000295

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00994

Gnomad4 SAS exome AF: 0.000285

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000142

Gnomad4 OTH exome AF: 0.00263

GnomAD4 genome AF: 0.000777 AC: 87 AN: 112012 Hom.: 0 Cov.: 23 AF XY: 0.000760 AC XY: 26 AN XY: 34206

Gnomad4 AFR AF: 0.000518

Gnomad4 AMR AF: 0.000473

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0178

Gnomad4 SAS AF: 0.000749

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000662

Alfa AF: 0.000356 Hom.: 0

Bravo AF: 0.000960

Asia WGS AF: 0.00995 AC: 25 AN: 2522

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, single submitter

Submissions by phenotype

Arts syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

X-linked nonsyndromic hearing loss Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Phosphoribosylpyrophosphate synthetase superactivity Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Charcot-Marie-Tooth, X-linked Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs768856537; hg19: chrX-106871705;