18-36187516-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_017947.4(MOCOS):c.-24G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 1,230,294 control chromosomes in the GnomAD database, including 291,256 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.63 (31537 hom., cov: 34)
  • Exomes 𝑓: 0.69 (259719 hom.)
• Consequence: MOCOS NM_017947.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.93

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]

COSMOC (HGNC:51610): (cell fate and sterol metabolism associated divergent transcript of MOCOS)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 18-36187516-G-A is Benign according to our data. Variant chr18-36187516-G-A is described in ClinVar as [Benign]. Clinvar id is 1258652.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr18-36187516-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MOCOS	NM_017947.4	c.-24G>A		5_prime_UTR_variant	1/15	ENST00000261326.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MOCOS	ENST00000261326.6	c.-24G>A		5_prime_UTR_variant	1/15	1	NM_017947.4	P1
COSMOC	ENST00000687261.2			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.633 AC: 96161 AN: 151946 Hom.: 31530 Cov.: 34

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.656

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.872

Gnomad SAS AF: 0.747

Gnomad FIN AF: 0.717

Gnomad MID AF: 0.764

Gnomad NFE AF: 0.698

Gnomad OTH AF: 0.662

GnomAD3 exomes AF: 0.695 AC: 3083 AN: 4436 Hom.: 1091 AF XY: 0.701 AC XY: 1813 AN XY: 2588

Gnomad AFR exome AF: 0.410

Gnomad AMR exome AF: 0.683

Gnomad ASJ exome AF: 0.628

Gnomad EAS exome AF: 0.902

Gnomad SAS exome AF: 0.750

Gnomad FIN exome AF: 0.733

Gnomad NFE exome AF: 0.706

Gnomad OTH exome AF: 0.681

GnomAD4 exome AF: 0.692 AC: 746350 AN: 1078236 Hom.: 259719 Cov.: 52 AF XY: 0.693 AC XY: 352979 AN XY: 509542

Gnomad4 AFR exome AF: 0.437

Gnomad4 AMR exome AF: 0.666

Gnomad4 ASJ exome AF: 0.682

Gnomad4 EAS exome AF: 0.872

Gnomad4 SAS exome AF: 0.745

Gnomad4 FIN exome AF: 0.713

Gnomad4 NFE exome AF: 0.692

Gnomad4 OTH exome AF: 0.684

GnomAD4 genome AF: 0.633 AC: 96193 AN: 152058 Hom.: 31537 Cov.: 34 AF XY: 0.638 AC XY: 47445 AN XY: 74326

Gnomad4 AFR AF: 0.448

Gnomad4 AMR AF: 0.656

Gnomad4 ASJ AF: 0.671

Gnomad4 EAS AF: 0.872

Gnomad4 SAS AF: 0.747

Gnomad4 FIN AF: 0.717

Gnomad4 NFE AF: 0.698

Gnomad4 OTH AF: 0.665

Alfa AF: 0.654 Hom.: 3950

Bravo AF: 0.620

Asia WGS AF: 0.803 AC: 2790 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	2.4
Dann	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11665282; hg19: chr18-33767479;