chr18-36187593-C-T

Variant names:

• chr18-36187593-C-T
• rs2144887356
• NM_017947.4:c.54C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_017947.4(MOCOS):​c.54C>T​(p.Ser18Ser) 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MOCOS NM_017947.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.588
• 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 -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 18-36187593-C-T is Benign according to our data. Variant chr18-36187593-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1571443.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.588 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.54C>T	p.Ser18Ser	synonymous	Exon 1 of 15	NP_060417.4	Q96EN8
	COSMOC	NR_134605.1		n.-158G>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.54C>T	p.Ser18Ser	synonymous	Exon 1 of 15	ENSP00000261326.4	Q96EN8
	MOCOS	ENST00000880903.1		c.54C>T	p.Ser18Ser	synonymous	Exon 1 of 16	ENSP00000550962.1
	MOCOS	ENST00000880908.1		c.54C>T	p.Ser18Ser	synonymous	Exon 1 of 14	ENSP00000550967.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1096132 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 520060

African (AFR) AF: 0.00 AC: 0 AN: 23452

American (AMR) AF: 0.00 AC: 0 AN: 9196

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14498

East Asian (EAS) AF: 0.00 AC: 0 AN: 27138

South Asian (SAS) AF: 0.00 AC: 0 AN: 22456

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23660

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3448

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 928048

Other (OTH) AF: 0.00 AC: 0 AN: 44236

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Xanthinuria type II (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	8.5
DANN	Benign	0.87
PhyloP100		0.59
PromoterAI		0.042	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: rs2144887356; hg19: chr18-33767556;