18-36187516-G-A

Variant names:

• chr18-36187516-G-A
• rs11665282
• NM_017947.4:c.-24G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.93
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -20 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_multiple_submitters_no_conflicts, 2 stars.
• 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 rank	MANE	Protein	UniProt
MOCOS	NM_017947.4	c.-24G>A		5_prime_UTR_variant	Exon 1 of 15	ENST00000261326.6	NP_060417.4
COSMOC	NR_134605.1	n.-81C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MOCOS	ENST00000261326.6	c.-24G>A		5_prime_UTR_variant	Exon 1 of 15	1	NM_017947.4	ENSP00000261326.4
COSMOC	ENST00000568654.3	n.-42C>T		upstream_gene_variant		1
COSMOC	ENST00000687261.3	n.-41C>T		upstream_gene_variant
COSMOC	ENST00000738210.1	n.-96C>T		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

GnomAD2 exomes AF: 0.695 AC: 3083 AN: 4436 AF XY: 0.701

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 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

African (AFR) AF: 0.437 AC: 9950 AN: 22768

American (AMR) AF: 0.666 AC: 5535 AN: 8316

Ashkenazi Jewish (ASJ) AF: 0.682 AC: 9691 AN: 14216

East Asian (EAS) AF: 0.872 AC: 22983 AN: 26350

South Asian (SAS) AF: 0.745 AC: 14746 AN: 19800

European-Finnish (FIN) AF: 0.713 AC: 15535 AN: 21798

Middle Eastern (MID) AF: 0.703 AC: 2057 AN: 2926

European-Non Finnish (NFE) AF: 0.692 AC: 636106 AN: 918586

Other (OTH) AF: 0.684 AC: 29747 AN: 43476

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

African (AFR) AF: 0.448 AC: 18591 AN: 41498

American (AMR) AF: 0.656 AC: 10030 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2329 AN: 3472

East Asian (EAS) AF: 0.872 AC: 4454 AN: 5108

South Asian (SAS) AF: 0.747 AC: 3606 AN: 4826

European-Finnish (FIN) AF: 0.717 AC: 7594 AN: 10590

Middle Eastern (MID) AF: 0.764 AC: 223 AN: 292

European-Non Finnish (NFE) AF: 0.698 AC: 47423 AN: 67946

Other (OTH) AF: 0.665 AC: 1408 AN: 2116

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	2.4
DANN	Benign	0.82
PhyloP100		-2.9
PromoterAI		-0.27	Neutral

Splicing

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

Other links and lift over

dbSNP: rs11665282; hg19: chr18-33767479;