18-36187535-G-A

Variant summary

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

The NM_017947.4(MOCOS):​c.-5G>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 0.0731 in 1,235,088 control chromosomes in the GnomAD database, including 3,643 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.054 ( 327 hom., cov: 34)
Exomes 𝑓: 0.076 ( 3316 hom. )

Consequence

MOCOS
NM_017947.4 5_prime_UTR

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -0.693
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]

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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 18-36187535-G-A is Benign according to our data. Variant chr18-36187535-G-A is described in ClinVar as [Benign]. Clinvar id is 1296803.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MOCOSNM_017947.4 linkuse as main transcriptc.-5G>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
MOCOSENST00000261326.6 linkuse as main transcriptc.-5G>A 5_prime_UTR_variant 1/151 NM_017947.4 ENSP00000261326 P1

Frequencies

GnomAD3 genomes
AF:
0.0537
AC:
8176
AN:
152138
Hom.:
327
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0151
Gnomad AMI
AF:
0.125
Gnomad AMR
AF:
0.0262
Gnomad ASJ
AF:
0.0445
Gnomad EAS
AF:
0.164
Gnomad SAS
AF:
0.0695
Gnomad FIN
AF:
0.0578
Gnomad MID
AF:
0.0414
Gnomad NFE
AF:
0.0732
Gnomad OTH
AF:
0.0449
GnomAD3 exomes
AF:
0.0761
AC:
673
AN:
8846
Hom.:
31
AF XY:
0.0761
AC XY:
375
AN XY:
4926
show subpopulations
Gnomad AFR exome
AF:
0.00977
Gnomad AMR exome
AF:
0.0437
Gnomad ASJ exome
AF:
0.0522
Gnomad EAS exome
AF:
0.197
Gnomad SAS exome
AF:
0.0672
Gnomad FIN exome
AF:
0.0429
Gnomad NFE exome
AF:
0.0844
Gnomad OTH exome
AF:
0.0692
GnomAD4 exome
AF:
0.0758
AC:
82093
AN:
1082838
Hom.:
3316
Cov.:
34
AF XY:
0.0758
AC XY:
38844
AN XY:
512262
show subpopulations
Gnomad4 AFR exome
AF:
0.0102
Gnomad4 AMR exome
AF:
0.0241
Gnomad4 ASJ exome
AF:
0.0434
Gnomad4 EAS exome
AF:
0.141
Gnomad4 SAS exome
AF:
0.0657
Gnomad4 FIN exome
AF:
0.0598
Gnomad4 NFE exome
AF:
0.0777
Gnomad4 OTH exome
AF:
0.0663
GnomAD4 genome
AF:
0.0537
AC:
8173
AN:
152250
Hom.:
327
Cov.:
34
AF XY:
0.0535
AC XY:
3982
AN XY:
74430
show subpopulations
Gnomad4 AFR
AF:
0.0150
Gnomad4 AMR
AF:
0.0261
Gnomad4 ASJ
AF:
0.0445
Gnomad4 EAS
AF:
0.164
Gnomad4 SAS
AF:
0.0695
Gnomad4 FIN
AF:
0.0578
Gnomad4 NFE
AF:
0.0732
Gnomad4 OTH
AF:
0.0444
Alfa
AF:
0.0304
Hom.:
20
Bravo
AF:
0.0509
Asia WGS
AF:
0.0760
AC:
264
AN:
3476

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 submitterclinical testingGeneDxNov 12, 2018- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
MOCOS-related disorder Benign:1
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesDec 05, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.72
CADD
Benign
6.6
DANN
Benign
0.77
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0

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.

Other links and lift over

dbSNP: rs117090508; hg19: chr18-33767498; API