18-36187497-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_017947.4(MOCOS):c.-43G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0365 in 1,226,352 control chromosomes in the GnomAD database, including 909 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.027 (70 hom., cov: 33)
  • Exomes 𝑓: 0.038 (839 hom.)
• Consequence: MOCOS NM_017947.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.172

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=-0.74).
• BP6: Variant 18-36187497-G-T is Benign according to our data. Variant chr18-36187497-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1203579.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0266 (4043/152150) while in subpopulation NFE AF= 0.0387 (2632/67978). AF 95% confidence interval is 0.0375. There are 70 homozygotes in gnomad4. There are 1881 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 70 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MOCOS	NM_017947.4	c.-43G>T		5_prime_UTR_variant	1/15	ENST00000261326.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MOCOS	ENST00000261326.6	c.-43G>T		5_prime_UTR_variant	1/15	1	NM_017947.4	P1
COSMOC	ENST00000568654.2			upstream_gene_variant		1
COSMOC	ENST00000687261.2			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0266 AC: 4048 AN: 152038 Hom.: 70 Cov.: 33

Gnomad AFR AF: 0.00794

Gnomad AMI AF: 0.0198

Gnomad AMR AF: 0.0355

Gnomad ASJ AF: 0.0450

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00891

Gnomad FIN AF: 0.0220

Gnomad MID AF: 0.0350

Gnomad NFE AF: 0.0387

Gnomad OTH AF: 0.0402

GnomAD3 exomes AF: 0.0390 AC: 95 AN: 2434 Hom.: 2 AF XY: 0.0331 AC XY: 48 AN XY: 1452

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.0357

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0246

Gnomad NFE exome AF: 0.0474

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0379 AC: 40686 AN: 1074202 Hom.: 839 Cov.: 29 AF XY: 0.0378 AC XY: 19180 AN XY: 507438

Gnomad4 AFR exome AF: 0.00583

Gnomad4 AMR exome AF: 0.0331

Gnomad4 ASJ exome AF: 0.0440

Gnomad4 EAS exome AF: 0.000115

Gnomad4 SAS exome AF: 0.00866

Gnomad4 FIN exome AF: 0.0272

Gnomad4 NFE exome AF: 0.0408

Gnomad4 OTH exome AF: 0.0337

GnomAD4 genome AF: 0.0266 AC: 4043 AN: 152150 Hom.: 70 Cov.: 33 AF XY: 0.0253 AC XY: 1881 AN XY: 74380

Gnomad4 AFR AF: 0.00787

Gnomad4 AMR AF: 0.0354

Gnomad4 ASJ AF: 0.0450

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00891

Gnomad4 FIN AF: 0.0220

Gnomad4 NFE AF: 0.0387

Gnomad4 OTH AF: 0.0398

Alfa AF: 0.0113 Hom.: 2

Bravo AF: 0.0273

Asia WGS AF: 0.00433 AC: 16 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 22, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	9.8
Dann	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs140350056; hg19: chr18-33767460;