chr18-36269905-G-T

Variant names:

• chr18-36269905-G-T
• rs529342
• NM_017947.4:c.*1220G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017947.4(MOCOS):​c.*1220G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 152,186 control chromosomes in the GnomAD database, including 47,660 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.79 (47658 hom., cov: 32)
  • Exomes 𝑓: 0.58 (2 hom.)
• Consequence: MOCOS NM_017947.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• xanthinuria type II

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017947.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOCOS	NM_017947.4	MANE Select	c.*1220G>T		3_prime_UTR	Exon 15 of 15	NP_060417.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOCOS	ENST00000261326.6	TSL:1 MANE Select	c.*1220G>T		3_prime_UTR	Exon 15 of 15	ENSP00000261326.4

Frequencies

GnomAD3 genomes AF: 0.787 AC: 119693 AN: 152054 Hom.: 47600 Cov.: 32

Gnomad AFR AF: 0.884

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.801

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.811

Gnomad SAS AF: 0.574

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.672

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.762

GnomAD4 exome AF: 0.583 AC: 7 AN: 12 Hom.: 2 Cov.: 0 AF XY: 0.500 AC XY: 4 AN XY: 8

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.750 AC: 6 AN: 8

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.787 AC: 119810 AN: 152174 Hom.: 47658 Cov.: 32 AF XY: 0.784 AC XY: 58316 AN XY: 74416

African (AFR) AF: 0.884 AC: 36708 AN: 41522

American (AMR) AF: 0.801 AC: 12247 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 2236 AN: 3472

East Asian (EAS) AF: 0.810 AC: 4180 AN: 5158

South Asian (SAS) AF: 0.574 AC: 2768 AN: 4822

European-Finnish (FIN) AF: 0.765 AC: 8108 AN: 10598

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.752 AC: 51165 AN: 68002

Other (OTH) AF: 0.761 AC: 1608 AN: 2112

Alfa AF: 0.750 Hom.: 49544

Bravo AF: 0.798

Asia WGS AF: 0.709 AC: 2468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.76
DANN	Benign	0.32
PhyloP100		0.012
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs529342; hg19: chr18-33849868;