18-36187693-G-GGGCA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_017947.4(MOCOS):c.142+16_142+19dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00131 in 1,265,070 control chromosomes in the GnomAD database, including 34 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0014 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0013 (31 hom.)
• Consequence: MOCOS NM_017947.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.107

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 -16 ACMG points.

• BP6: Variant 18-36187693-G-GGGCA is Benign according to our data. Variant chr18-36187693-G-GGGCA is described in ClinVar as [Likely_benign]. Clinvar id is 1589614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00136 (207/152330) while in subpopulation EAS AF= 0.024 (124/5168). AF 95% confidence interval is 0.0206. There are 3 homozygotes in gnomad4. There are 120 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MOCOS	NM_017947.4	c.142+16_142+19dup		intron_variant		ENST00000261326.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MOCOS	ENST00000261326.6	c.142+16_142+19dup		intron_variant		1	NM_017947.4	P1

Frequencies

GnomAD3 genomes AF: 0.00134 AC: 204 AN: 152218 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.0239

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00433

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00209 AC: 84 AN: 40170 Hom.: 1 AF XY: 0.00187 AC XY: 42 AN XY: 22438

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00472

Gnomad EAS exome AF: 0.0223

Gnomad SAS exome AF: 0.00115

Gnomad FIN exome AF: 0.00220

Gnomad NFE exome AF: 0.000154

Gnomad OTH exome AF: 0.00135

GnomAD4 exome AF: 0.00130 AC: 1451 AN: 1112740 Hom.: 31 Cov.: 33 AF XY: 0.00131 AC XY: 693 AN XY: 529304

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00224

Gnomad4 EAS exome AF: 0.0403

Gnomad4 SAS exome AF: 0.00112

Gnomad4 FIN exome AF: 0.00271

Gnomad4 NFE exome AF: 0.000103

Gnomad4 OTH exome AF: 0.00156

GnomAD4 genome AF: 0.00136 AC: 207 AN: 152330 Hom.: 3 Cov.: 33 AF XY: 0.00161 AC XY: 120 AN XY: 74472

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000653

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.0240

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.00433

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.000324 Hom.: 0

Bravo AF: 0.00110

Asia WGS AF: 0.0140 AC: 49 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Xanthinuria type II Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Jul 26, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 08, 2024	- -

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: rs780090086; hg19: chr18-33767656;