18-36187554-G-C

Variant names:

• chr18-36187554-G-C
• rs145568479
• NM_017947.4:c.15G>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_017947.4(MOCOS):​c.15G>C​(p.Ala5Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A5A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MOCOS NM_017947.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60
• Publications: 0 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]

COSMOC (HGNC:51610): (cell fate and sterol metabolism associated divergent transcript of MOCOS)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP7: Synonymous conserved (PhyloP=-1.6 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOCOS	NM_017947.4	c.15G>C	p.Ala5Ala	synonymous_variant	Exon 1 of 15	ENST00000261326.6	NP_060417.4
COSMOC	NR_134605.1	n.-119C>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MOCOS	ENST00000261326.6	c.15G>C	p.Ala5Ala	synonymous_variant	Exon 1 of 15	1	NM_017947.4	ENSP00000261326.4
COSMOC	ENST00000568654.3	n.-80C>G		upstream_gene_variant		1
COSMOC	ENST00000687261.3	n.-79C>G		upstream_gene_variant
COSMOC	ENST00000738210.1	n.-134C>G		upstream_gene_variant

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1087604 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 515064

African (AFR) AF: 0.00 AC: 0 AN: 23170

American (AMR) AF: 0.00 AC: 0 AN: 8946

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14344

East Asian (EAS) AF: 0.00 AC: 0 AN: 26852

South Asian (SAS) AF: 0.00 AC: 0 AN: 20600

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22946

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3072

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 923774

Other (OTH) AF: 0.00 AC: 0 AN: 43900

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	3.6
DANN	Benign	0.49
PhyloP100		-1.6
PromoterAI		-0.039	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1

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: rs145568479; hg19: chr18-33767517;