18-36269905-G-T

Position:

• chr18-36269905-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MOCOS	NM_017947.4	c.*1220G>T		3_prime_UTR_variant	15/15	ENST00000261326.6	NP_060417.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MOCOS	ENST00000261326.6	c.*1220G>T		3_prime_UTR_variant	15/15	1	NM_017947.4	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

Gnomad4 NFE exome AF: 0.750

Gnomad4 OTH exome AF: 0.250

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

Gnomad4 AFR AF: 0.884

Gnomad4 AMR AF: 0.801

Gnomad4 ASJ AF: 0.644

Gnomad4 EAS AF: 0.810

Gnomad4 SAS AF: 0.574

Gnomad4 FIN AF: 0.765

Gnomad4 NFE AF: 0.752

Gnomad4 OTH AF: 0.761

Alfa AF: 0.744 Hom.: 35780

Bravo AF: 0.798

Asia WGS AF: 0.709 AC: 2468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.76
DANN	Benign	0.32

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

Other links and lift over

dbSNP: rs529342; hg19: chr18-33849868;