Variant chr18-36187605-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_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. 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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MOCOS	NM_017947.4 linkuse as main transcript	c.66C>A	p.Ser22Arg	missense_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.66C>A	p.Ser22Arg	missense_variant	1/15	1	NM_017947.4	ENSP00000261326	P1

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

GnomAD3 exomes

AF:

0.0820

AC:

1434

AN:

17482

Hom.:

AF XY:

0.0864

AC XY:

845

AN XY:

9780

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 SAS exome

AF:

0.0323

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

Gnomad4 AFR exome

AF:

0.0231

Gnomad4 AMR exome

AF:

0.0658

Gnomad4 ASJ exome

AF:

0.162

Gnomad4 EAS exome

AF:

0.000662

Gnomad4 SAS exome

AF:

0.0348

Gnomad4 FIN exome

AF:

0.0906

Gnomad4 NFE exome

AF:

0.0927

Gnomad4 OTH exome

AF:

0.0866

GnomAD4 genome

AF:

0.0694

AC:

10569

AN:

152286

Hom.:

438

Cov.:

AF XY:

0.0680

AC XY:

5063

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0261

Gnomad4 AMR

AF:

0.0680

Gnomad4 ASJ

AF:

0.168

Gnomad4 EAS

AF:

0.00369

Gnomad4 SAS

AF:

0.0337

Gnomad4 FIN

AF:

0.0814

Gnomad4 NFE

AF:

0.0950

Gnomad4 OTH

AF:

0.0964

Alfa

AF:

0.0595

Hom.:

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Xanthinuria type II

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

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

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

MutationTaster

Benign

1.0

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

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.10

gMVP

0.34

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