18-36187605-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017947.4(MOCOS):​c.66C>G​(p.Ser22Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000912 in 1,096,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 9.1e-7 (0 hom.)
• Consequence: MOCOS NM_017947.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.311
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18814933).

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>G	p.Ser22Arg	missense	Exon 1 of 15	NP_060417.4	Q96EN8
	COSMOC	NR_134605.1		n.-170G>C		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>G	p.Ser22Arg	missense	Exon 1 of 15	ENSP00000261326.4	Q96EN8
	MOCOS	ENST00000880903.1		c.66C>G	p.Ser22Arg	missense	Exon 1 of 16	ENSP00000550962.1
	MOCOS	ENST00000880908.1		c.66C>G	p.Ser22Arg	missense	Exon 1 of 14	ENSP00000550967.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 9.12e-7 AC: 1 AN: 1096698 Hom.: 0 Cov.: 34 AF XY: 0.00000192 AC XY: 1 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: 0.00000108 AC: 1 AN: 928232

Other (OTH) AF: 0.00 AC: 0 AN: 44284

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.035	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.34	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.31
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.035
Sift	Benign	0.056	T
Sift4G	Uncertain	0.013	D
Polyphen		0.97	D
Vest4		0.15
MutPred		0.31		Loss of phosphorylation at S22 (P = 0.0115)
MVP		0.25
MPC		2.5
ClinPred		0.71	D
GERP RS		2.0
PromoterAI		0.097	Neutral
Varity_R		0.10
gMVP		0.34
Mutation Taster		=97/3	polymorphism

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;