rs779808561

Variant names:

• chr18-36187579-A-C
• rs779808561
• NM_017947.4:c.40A>C

Your query was ambiguous. Multiple possible variants found:

• chr18-36187579-A-C
• chr18-36187579-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_017947.4(MOCOS):​c.40A>C​(p.Thr14Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,094,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. T14S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: MOCOS NM_017947.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.127
• Publications: 1 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054133594).

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.40A>C	p.Thr14Pro	missense	Exon 1 of 15	NP_060417.4	Q96EN8
	COSMOC	NR_134605.1		n.-144T>G		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.40A>C	p.Thr14Pro	missense	Exon 1 of 15	ENSP00000261326.4	Q96EN8
	MOCOS	ENST00000880903.1		c.40A>C	p.Thr14Pro	missense	Exon 1 of 16	ENSP00000550962.1
	MOCOS	ENST00000880908.1		c.40A>C	p.Thr14Pro	missense	Exon 1 of 14	ENSP00000550967.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000274 AC: 3 AN: 1094630 Hom.: 0 Cov.: 34 AF XY: 0.00000193 AC XY: 1 AN XY: 519240

African (AFR) AF: 0.00 AC: 0 AN: 23424

American (AMR) AF: 0.00 AC: 0 AN: 9302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14474

East Asian (EAS) AF: 0.00 AC: 0 AN: 27120

South Asian (SAS) AF: 0.00 AC: 0 AN: 21956

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3312

European-Non Finnish (NFE) AF: 0.00000324 AC: 3 AN: 927258

Other (OTH) AF: 0.00 AC: 0 AN: 44168

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.5
DANN	Benign	0.37
DEOGEN2	Benign	0.034	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.18	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.34	N
PhyloP100		0.13
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.93	N
REVEL	Benign	0.013
Sift	Benign	0.19	T
Sift4G	Benign	0.32	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.20		Gain of helix (P = 0.0696)
MVP		0.21
MPC		1.8
ClinPred		0.028	T
GERP RS		-0.27
PromoterAI		0.058	Neutral
Varity_R		0.20
gMVP		0.39
Mutation Taster		=96/4	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: rs779808561; hg19: chr18-33767542;