dbSNP rs751964724: MOCOS:p.Ala2Asp (chr18-36187544-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017947.4(MOCOS):c.5C>A(p.Ala2Asp) variant causes a missense 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. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A2V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MOCOS
NM_017947.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.99

Publications

0 publications found

Variant links:

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]

MOCOS links:

COSMOC (HGNC:51610): (cell fate and sterol metabolism associated divergent transcript of MOCOS)

COSMOC links:

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ACMG classification

Classification was made for transcript

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=0.20438692).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOCOS	NM_017947.4 link	c.5C>A	p.Ala2Asp	missense_variant	Exon 1 of 15	ENST00000261326.6	NP_060417.4	Q96EN8
COSMOC	NR_134605.1 link	n.-109G>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MOCOS	ENST00000261326.6 link	c.5C>A	p.Ala2Asp	missense_variant	Exon 1 of 15	1	NM_017947.4	ENSP00000261326.4	Q96EN8
COSMOC	ENST00000568654.3 link	n.-70G>T		upstream_gene_variant		1
COSMOC	ENST00000687261.3 link	n.-69G>T		upstream_gene_variant
COSMOC	ENST00000738210.1 link	n.-124G>T		upstream_gene_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

11162

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

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1084904

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

513492

African (AFR)

AF:

0.00

AC:

AN:

23052

American (AMR)

AF:

0.00

AC:

AN:

8726

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14308

East Asian (EAS)

AF:

0.00

AC:

AN:

26696

South Asian (SAS)

AF:

0.00

AC:

AN:

20466

European-Finnish (FIN)

AF:

0.00

AC:

AN:

22706

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3006

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

922172

Other (OTH)

AF:

0.00

AC:

AN:

43772

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000124

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.019

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.38

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.32

M_CAP

Benign

0.072

MetaRNN

Benign

0.20

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

PhyloP100

2.0

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-0.68

REVEL

Benign

0.045

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.24

Vest4

0.26

MutPred

0.19

Loss of catalytic residue at A2 (P = 0.1252);

MVP

0.37

MPC

2.1

ClinPred

0.88

GERP RS

3.2

PromoterAI

-0.35

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.46

gMVP

0.53

Mutation Taster

=94/6

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over