18-36187585-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017947.4(MOCOS):​c.46G>T​(p.Ala16Ser) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A16V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

MOCOS
NM_017947.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.928

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

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ACMG classification

Classification was made for transcript

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=0.04824567).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MOCOSNM_017947.4 linkc.46G>T p.Ala16Ser missense_variant Exon 1 of 15 ENST00000261326.6 NP_060417.4 Q96EN8
COSMOCNR_134605.1 linkn.-150C>A upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MOCOSENST00000261326.6 linkc.46G>T p.Ala16Ser missense_variant Exon 1 of 15 1 NM_017947.4 ENSP00000261326.4 Q96EN8
COSMOCENST00000568654.3 linkn.-111C>A upstream_gene_variant 1
COSMOCENST00000687261.3 linkn.-110C>A upstream_gene_variant
COSMOCENST00000738210.1 linkn.-165C>A upstream_gene_variant

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1095400
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
519642
African (AFR)
AF:
0.00
AC:
0
AN:
23444
American (AMR)
AF:
0.00
AC:
0
AN:
9266
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
14486
East Asian (EAS)
AF:
0.00
AC:
0
AN:
27136
South Asian (SAS)
AF:
0.00
AC:
0
AN:
22254
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
23656
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3360
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
927586
Other (OTH)
AF:
0.00
AC:
0
AN:
44212
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 06, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.46G>T (p.A16S) alteration is located in exon 1 (coding exon 1) of the MOCOS gene. This alteration results from a G to T substitution at nucleotide position 46, causing the alanine (A) at amino acid position 16 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.082
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.79
CADD
Benign
0.28
DANN
Benign
0.71
DEOGEN2
Benign
0.017
T
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.15
N
LIST_S2
Benign
0.30
T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.048
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.6
L
PhyloP100
-0.93
PrimateAI
Uncertain
0.65
T
PROVEAN
Benign
-0.050
N
REVEL
Benign
0.036
Sift
Benign
0.34
T
Sift4G
Benign
0.46
T
Polyphen
0.0
B
Vest4
0.10
MutPred
0.22
Gain of helix (P = 0.0117);
MVP
0.16
MPC
1.4
ClinPred
0.090
T
GERP RS
-1.6
PromoterAI
0.058
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.12
gMVP
0.15
Mutation Taster
=98/2
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

Publications

Other links and lift over

hg19: chr18-33767548; API