18-36187605-C-T

Variant names:

• chr18-36187605-C-T
• rs113873219
• NM_017947.4:c.66C>T

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.66C>T​(p.Ser22Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,096,696 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 34)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: MOCOS NM_017947.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.311
• Publications: 12 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=-0.56).
• BP7: Synonymous conserved (PhyloP=-0.311 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOCOS	NM_017947.4	MANE Select	c.66C>T	p.Ser22Ser	synonymous	Exon 1 of 15	NP_060417.4	Q96EN8
	COSMOC	NR_134605.1		n.-170G>A		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOCOS	ENST00000261326.6	TSL:1 MANE Select	c.66C>T	p.Ser22Ser	synonymous	Exon 1 of 15	ENSP00000261326.4	Q96EN8
	MOCOS	ENST00000880903.1		c.66C>T	p.Ser22Ser	synonymous	Exon 1 of 16	ENSP00000550962.1
	MOCOS	ENST00000880908.1		c.66C>T	p.Ser22Ser	synonymous	Exon 1 of 14	ENSP00000550967.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00 AC: 0 AN: 17482 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000821 AC: 9 AN: 1096696 Hom.: 0 Cov.: 34 AF XY: 0.0000154 AC XY: 8 AN XY: 520420

African (AFR) AF: 0.00 AC: 0 AN: 23458

American (AMR) AF: 0.00 AC: 0 AN: 9116

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14504

East Asian (EAS) AF: 0.00 AC: 0 AN: 27196

South Asian (SAS) AF: 0.00 AC: 0 AN: 22740

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3544

European-Non Finnish (NFE) AF: 0.00000862 AC: 8 AN: 928230

Other (OTH) AF: 0.0000226 AC: 1 AN: 44284

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 143

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	7.9
DANN	Benign	0.94
PhyloP100		-0.31
PromoterAI		0.064	Neutral
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

Other links and lift over

dbSNP: rs113873219; hg19: chr18-33767568;