Variant 18-36187692-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_017947.4(MOCOS):c.142+11C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0198 in 1,264,752 control chromosomes in the GnomAD database, including 318 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 27 hom., cov: 33)

Exomes 𝑓: 0.021 ( 291 hom. )

Consequence

MOCOS
NM_017947.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.97

Variant links:

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]

MOCOS links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 18-36187692-C-A is Benign according to our data. Variant chr18-36187692-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1167027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0138 (2105/152274) while in subpopulation NFE AF= 0.0213 (1445/67996). AF 95% confidence interval is 0.0203. There are 27 homozygotes in gnomad4. There are 928 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MOCOS	NM_017947.4 linkuse as main transcript	c.142+11C>A		intron_variant		ENST00000261326.6	NP_060417.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MOCOS	ENST00000261326.6 linkuse as main transcript	c.142+11C>A		intron_variant		1	NM_017947.4	ENSP00000261326	P1

Frequencies

GnomAD3 genomes

AF:

0.0139

AC:

2108

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00345

Gnomad AMI

AF:

0.0428

Gnomad AMR

AF:

0.0183

Gnomad ASJ

AF:

0.0254

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00310

Gnomad FIN

AF:

0.00414

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0212

Gnomad OTH

AF:

0.0177

GnomAD3 exomes

AF:

0.0162

AC:

652

AN:

40344

Hom.:

AF XY:

0.0171

AC XY:

385

AN XY:

22504

show subpopulations

Gnomad AFR exome

AF:

0.00410

Gnomad AMR exome

AF:

0.0147

Gnomad ASJ exome

AF:

0.0288

Gnomad EAS exome

AF:

0.000317

Gnomad SAS exome

AF:

0.00452

Gnomad FIN exome

AF:

0.00291

Gnomad NFE exome

AF:

0.0213

Gnomad OTH exome

AF:

0.0135

GnomAD4 exome

AF:

0.0206

AC:

22970

AN:

1112478

Hom.:

291

Cov.:

AF XY:

0.0203

AC XY:

10759

AN XY:

529146

show subpopulations

Gnomad4 AFR exome

AF:

0.00333

Gnomad4 AMR exome

AF:

0.0155

Gnomad4 ASJ exome

AF:

0.0230

Gnomad4 EAS exome

AF:

0.0000347

Gnomad4 SAS exome

AF:

0.00365

Gnomad4 FIN exome

AF:

0.00387

Gnomad4 NFE exome

AF:

0.0227

Gnomad4 OTH exome

AF:

0.0179

GnomAD4 genome

AF:

0.0138

AC:

2105

AN:

152274

Hom.:

Cov.:

AF XY:

0.0125

AC XY:

928

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00344

Gnomad4 AMR

AF:

0.0183

Gnomad4 ASJ

AF:

0.0254

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.00414

Gnomad4 NFE

AF:

0.0213

Gnomad4 OTH

AF:

0.0175

Alfa

AF:

0.0160

Hom.:

Bravo

AF:

0.0145

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 12, 2021	- -

Xanthinuria type II

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

1.5

DANN

Benign

0.94

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over