rs113873219

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr18-36187605-C-A
• chr18-36187605-C-G
• chr18-36187605-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017947.4(MOCOS):​c.66C>A​(p.Ser22Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0859 in 1,248,948 control chromosomes in the GnomAD database, including 5,035 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.069 (438 hom., cov: 34)
  • Exomes 𝑓: 0.088 (4597 hom.)
• Consequence: MOCOS NM_017947.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015840232).
• BP6: Variant 18-36187605-C-A is Benign according to our data. Variant chr18-36187605-C-A is described in ClinVar as Benign. ClinVar VariationId is 1168080.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.093 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOCOS	NM_017947.4	MANE Select	c.66C>A	p.Ser22Arg	missense	Exon 1 of 15	NP_060417.4	Q96EN8
	COSMOC	NR_134605.1		n.-170G>T		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>A	p.Ser22Arg	missense	Exon 1 of 15	ENSP00000261326.4	Q96EN8
	MOCOS	ENST00000880903.1		c.66C>A	p.Ser22Arg	missense	Exon 1 of 16	ENSP00000550962.1
	MOCOS	ENST00000880908.1		c.66C>A	p.Ser22Arg	missense	Exon 1 of 14	ENSP00000550967.1

Frequencies

GnomAD3 genomes AF: 0.0695 AC: 10580 AN: 152176 Hom.: 438 Cov.: 34

Gnomad AFR AF: 0.0263

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.0681

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.00368

Gnomad SAS AF: 0.0337

Gnomad FIN AF: 0.0814

Gnomad MID AF: 0.0924

Gnomad NFE AF: 0.0950

Gnomad OTH AF: 0.0979

GnomAD2 exomes AF: 0.0820 AC: 1434 AN: 17482 AF XY: 0.0864

Gnomad AFR exome AF: 0.0256

Gnomad AMR exome AF: 0.0453

Gnomad ASJ exome AF: 0.168

Gnomad EAS exome AF: 0.00111

Gnomad FIN exome AF: 0.0792

Gnomad NFE exome AF: 0.0963

Gnomad OTH exome AF: 0.118

GnomAD4 exome AF: 0.0882 AC: 96716 AN: 1096662 Hom.: 4597 Cov.: 34 AF XY: 0.0889 AC XY: 46275 AN XY: 520404

African (AFR) AF: 0.0231 AC: 542 AN: 23456

American (AMR) AF: 0.0658 AC: 600 AN: 9112

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 2347 AN: 14502

East Asian (EAS) AF: 0.000662 AC: 18 AN: 27196

South Asian (SAS) AF: 0.0348 AC: 792 AN: 22734

European-Finnish (FIN) AF: 0.0906 AC: 2139 AN: 23620

Middle Eastern (MID) AF: 0.113 AC: 399 AN: 3542

European-Non Finnish (NFE) AF: 0.0927 AC: 86045 AN: 928216

Other (OTH) AF: 0.0866 AC: 3834 AN: 44284

GnomAD4 genome AF: 0.0694 AC: 10569 AN: 152286 Hom.: 438 Cov.: 34 AF XY: 0.0680 AC XY: 5063 AN XY: 74448

African (AFR) AF: 0.0261 AC: 1087 AN: 41578

American (AMR) AF: 0.0680 AC: 1040 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 582 AN: 3472

East Asian (EAS) AF: 0.00369 AC: 19 AN: 5152

South Asian (SAS) AF: 0.0337 AC: 163 AN: 4830

European-Finnish (FIN) AF: 0.0814 AC: 865 AN: 10624

Middle Eastern (MID) AF: 0.0890 AC: 26 AN: 292

European-Non Finnish (NFE) AF: 0.0950 AC: 6458 AN: 68012

Other (OTH) AF: 0.0964 AC: 204 AN: 2116

Alfa AF: 0.0671 Hom.: 143

Bravo AF: 0.0690

TwinsUK AF: 0.101 AC: 373

ALSPAC AF: 0.0942 AC: 363

ESP6500AA AF: 0.0219 AC: 76

ESP6500EA AF: 0.0771 AC: 538

ExAC AF: 0.0426 AC: 3974

Asia WGS AF: 0.0210 AC: 73 AN: 3474

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Xanthinuria type II (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.63	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	0.17	N
LIST_S2	Benign	0.34	T
MetaRNN	Benign	0.0016	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	0.034
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)
MPC		2.5
ClinPred		0.022	T
GERP RS		2.0
PromoterAI		0.11	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.10
gMVP		0.34
Mutation Taster		=97/3	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: rs113873219; hg19: chr18-33767568; COSMIC: COSV54340658; COSMIC: COSV54340658;