18-36187692-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_017947.4(MOCOS):c.142+11C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0198 in 1,264,752 control chromosomes in the GnomAD database, including 318 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (27 hom., cov: 33)
  • Exomes 𝑓: 0.021 (291 hom.)
• Consequence: MOCOS NM_017947.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.97

Genes affected

MOCOS (HGNC:18234): (molybdenum cofactor sulfurase) This gene encodes an enzyme that sulfurates the molybdenum cofactor which is required for activation of the xanthine dehydrogenase (XDH) and aldehyde oxidase (AO) enzymes. XDH catalyzes the conversion of hypoxanthine to uric acid via xanthine, as well as the conversion of allopurinol to oxypurinol, and pyrazinamide to 5-hydroxy pyrazinamide. Mutations in this gene cause the metabolic disorder classical xanthinuria type II which is characterized by the loss of XDH/XO and AO enzyme activity, decreased levels of uric acid in the urine, increased levels of xanthine and hypoxanthine in the serum and urine, formation of xanthine stones in the urinary tract, and myositis due to tissue deposition of xanthine. [provided by RefSeq, Apr 2017]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 18-36187692-C-A is Benign according to our data. Variant chr18-36187692-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1167027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0138 (2105/152274) while in subpopulation NFE AF= 0.0213 (1445/67996). AF 95% confidence interval is 0.0203. There are 27 homozygotes in gnomad4. There are 928 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MOCOS	NM_017947.4	c.142+11C>A		intron_variant		ENST00000261326.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MOCOS	ENST00000261326.6	c.142+11C>A		intron_variant		1	NM_017947.4	P1

Frequencies

GnomAD3 genomes AF: 0.0139 AC: 2108 AN: 152162 Hom.: 27 Cov.: 33

Gnomad AFR AF: 0.00345

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0183

Gnomad ASJ AF: 0.0254

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00310

Gnomad FIN AF: 0.00414

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0212

Gnomad OTH AF: 0.0177

GnomAD3 exomes AF: 0.0162 AC: 652 AN: 40344 Hom.: 4 AF XY: 0.0171 AC XY: 385 AN XY: 22504

Gnomad AFR exome AF: 0.00410

Gnomad AMR exome AF: 0.0147

Gnomad ASJ exome AF: 0.0288

Gnomad EAS exome AF: 0.000317

Gnomad SAS exome AF: 0.00452

Gnomad FIN exome AF: 0.00291

Gnomad NFE exome AF: 0.0213

Gnomad OTH exome AF: 0.0135

GnomAD4 exome AF: 0.0206 AC: 22970 AN: 1112478 Hom.: 291 Cov.: 33 AF XY: 0.0203 AC XY: 10759 AN XY: 529146

Gnomad4 AFR exome AF: 0.00333

Gnomad4 AMR exome AF: 0.0155

Gnomad4 ASJ exome AF: 0.0230

Gnomad4 EAS exome AF: 0.0000347

Gnomad4 SAS exome AF: 0.00365

Gnomad4 FIN exome AF: 0.00387

Gnomad4 NFE exome AF: 0.0227

Gnomad4 OTH exome AF: 0.0179

GnomAD4 genome AF: 0.0138 AC: 2105 AN: 152274 Hom.: 27 Cov.: 33 AF XY: 0.0125 AC XY: 928 AN XY: 74448

Gnomad4 AFR AF: 0.00344

Gnomad4 AMR AF: 0.0183

Gnomad4 ASJ AF: 0.0254

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00290

Gnomad4 FIN AF: 0.00414

Gnomad4 NFE AF: 0.0213

Gnomad4 OTH AF: 0.0175

Alfa AF: 0.0160 Hom.: 4

Bravo AF: 0.0145

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 12, 2021

- -

Xanthinuria type II Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	1.5
Dann	Benign	0.94

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: rs141031604; hg19: chr18-33767655;