18-36187605-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017947.4(MOCOS):c.66C>A(p.Ser22Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0859 in 1,248,948 control chromosomes in the GnomAD database, including 5,035 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.069 ( 438 hom., cov: 34)

Exomes 𝑓: 0.088 ( 4597 hom. )

Consequence

MOCOS
NM_017947.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.311

Publications

12 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015840232).

BP6

Variant 18-36187605-C-A is Benign according to our data. Variant chr18-36187605-C-A is described in ClinVar as [Benign]. Clinvar id is 1168080.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.093 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOCOS	NM_017947.4 link	c.66C>A	p.Ser22Arg	missense_variant	Exon 1 of 15	ENST00000261326.6	NP_060417.4	Q96EN8
COSMOC	NR_134605.1 link	n.-170G>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MOCOS	ENST00000261326.6 link	c.66C>A	p.Ser22Arg	missense_variant	Exon 1 of 15	1	NM_017947.4	ENSP00000261326.4	Q96EN8
COSMOC	ENST00000568654.3 link	n.-131G>T		upstream_gene_variant		1
COSMOC	ENST00000687261.3 link	n.-130G>T		upstream_gene_variant
COSMOC	ENST00000738210.1 link	n.-185G>T		upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.0695

AC:

10580

AN:

152176

Hom.:

438

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0263

Gnomad AMI

AF:

0.137

Gnomad AMR

AF:

0.0681

Gnomad ASJ

AF:

0.168

Gnomad EAS

AF:

0.00368

Gnomad SAS

AF:

0.0337

Gnomad FIN

AF:

0.0814

Gnomad MID

AF:

0.0924

Gnomad NFE

AF:

0.0950

Gnomad OTH

AF:

0.0979

GnomAD2 exomes

AF:

0.0820

AC:

1434

AN:

17482

AF XY:

0.0864

show subpopulations

Gnomad AFR exome

AF:

0.0256

Gnomad AMR exome

AF:

0.0453

Gnomad ASJ exome

AF:

0.168

Gnomad EAS exome

AF:

0.00111

Gnomad FIN exome

AF:

0.0792

Gnomad NFE exome

AF:

0.0963

Gnomad OTH exome

AF:

0.118

GnomAD4 exome

AF:

0.0882

AC:

96716

AN:

1096662

Hom.:

4597

Cov.:

AF XY:

0.0889

AC XY:

46275

AN XY:

520404

show subpopulations

African (AFR)

AF:

0.0231

AC:

542

AN:

23456

American (AMR)

AF:

0.0658

AC:

600

AN:

9112

Ashkenazi Jewish (ASJ)

AF:

0.162

AC:

2347

AN:

14502

East Asian (EAS)

AF:

0.000662

AC:

AN:

27196

South Asian (SAS)

AF:

0.0348

AC:

792

AN:

22734

European-Finnish (FIN)

AF:

0.0906

AC:

2139

AN:

23620

Middle Eastern (MID)

AF:

0.113

AC:

399

AN:

3542

European-Non Finnish (NFE)

AF:

0.0927

AC:

86045

AN:

928216

Other (OTH)

AF:

0.0866

AC:

3834

AN:

44284

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

5552

11104

16655

22207

27759

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0694

AC:

10569

AN:

152286

Hom.:

438

Cov.:

AF XY:

0.0680

AC XY:

5063

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.0261

AC:

1087

AN:

41578

American (AMR)

AF:

0.0680

AC:

1040

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.168

AC:

582

AN:

3472

East Asian (EAS)

AF:

0.00369

AC:

AN:

5152

South Asian (SAS)

AF:

0.0337

AC:

163

AN:

4830

European-Finnish (FIN)

AF:

0.0814

AC:

865

AN:

10624

Middle Eastern (MID)

AF:

0.0890

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0950

AC:

6458

AN:

68012

Other (OTH)

AF:

0.0964

AC:

204

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

505

1010

1516

2021

2526

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0671

Hom.:

143

Bravo

AF:

0.0690

TwinsUK

AF:

0.101

AC:

373

ALSPAC

AF:

0.0942

AC:

363

ESP6500AA

AF:

0.0219

AC:

ESP6500EA

AF:

0.0771

AC:

538

ExAC

AF:

0.0426

AC:

3974

Asia WGS

AF:

0.0210

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

- -

Xanthinuria type II

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.035

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.34

MetaRNN

Benign

0.0016

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.1

PhyloP100

-0.31

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-1.4

REVEL

Benign

0.034

Sift

Benign

0.056

Sift4G

Uncertain

0.013

Polyphen

0.97

Vest4

0.15

MutPred

0.31

Loss of phosphorylation at S22 (P = 0.0115);

MPC

2.5

ClinPred

0.022

GERP RS

2.0

PromoterAI

0.11

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.10

gMVP

0.34

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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18-36187605-C-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over