Variant chr18-36187516-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.93

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:

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

COSMOC 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=-0.72).

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. 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	Protein	UniProt
MOCOS	NM_017947.4 linkuse as main transcript	c.-24G>A		5_prime_UTR_variant	1/15	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.-24G>A		5_prime_UTR_variant	1/15	1	NM_017947.4	ENSP00000261326	P1
COSMOC	ENST00000687261.2 linkuse as main transcript			upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.633

AC:

96161

AN:

151946

Hom.:

31530

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.693

AC XY:

352979

AN XY:

509542

show subpopulations

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.:

AF XY:

0.638

AC XY:

47445

AN XY:

74326

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

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