chr18-36194987-G-A

Position:

• chr18-36194987-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.143-270G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 152,150 control chromosomes in the GnomAD database, including 3,689 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.20 (3689 hom., cov: 33)
• Consequence: MOCOS NM_017947.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.15

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 18-36194987-G-A is Benign according to our data. Variant chr18-36194987-G-A is described in ClinVar as [Benign]. Clinvar id is 1262514.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MOCOS	NM_017947.4	c.143-270G>A		intron_variant		ENST00000261326.6	NP_060417.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MOCOS	ENST00000261326.6	c.143-270G>A		intron_variant		1	NM_017947.4	ENSP00000261326	P1

Frequencies

GnomAD3 genomes AF: 0.197 AC: 30001 AN: 152032 Hom.: 3687 Cov.: 33

Gnomad AFR AF: 0.0652

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.234

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.197 AC: 30004 AN: 152150 Hom.: 3689 Cov.: 33 AF XY: 0.201 AC XY: 14963 AN XY: 74366

Gnomad4 AFR AF: 0.0651

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.280

Gnomad4 EAS AF: 0.391

Gnomad4 SAS AF: 0.381

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.235

Alfa AF: 0.202 Hom.: 456

Bravo AF: 0.189

Asia WGS AF: 0.388 AC: 1345 AN: 3478

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	-0.92
CADD	Benign	0.19
DANN	Benign	0.61

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: rs8093132; hg19: chr18-33774950;