GeneBe

18-36187516-G-T

Variant names:

Variant summary

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

The NM_017947.4(MOCOS):​c.-24G>T variant causes a 5 prime UTR premature start codon gain 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

MOCOS
NM_017947.4 5_prime_UTR_premature_start_codon_gain

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.93

Publications

12 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 (BayesDel_noAF=-0.73).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MOCOSNM_017947.4 linkc.-24G>T 5_prime_UTR_premature_start_codon_gain_variant Exon 1 of 15 ENST00000261326.6 NP_060417.4 Q96EN8
MOCOSNM_017947.4 linkc.-24G>T 5_prime_UTR_variant Exon 1 of 15 ENST00000261326.6 NP_060417.4 Q96EN8
COSMOCNR_134605.1 linkn.-81C>A upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MOCOSENST00000261326.6 linkc.-24G>T 5_prime_UTR_premature_start_codon_gain_variant Exon 1 of 15 1 NM_017947.4 ENSP00000261326.4 Q96EN8
MOCOSENST00000261326.6 linkc.-24G>T 5_prime_UTR_variant Exon 1 of 15 1 NM_017947.4 ENSP00000261326.4 Q96EN8

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1078290
Hom.:
0
Cov.:
52
AF XY:
0.00
AC XY:
0
AN XY:
509580
African (AFR)
AF:
0.00
AC:
0
AN:
22768
American (AMR)
AF:
0.00
AC:
0
AN:
8316
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
14216
East Asian (EAS)
AF:
0.00
AC:
0
AN:
26352
South Asian (SAS)
AF:
0.00
AC:
0
AN:
19802
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
21810
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
2926
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
918624
Other (OTH)
AF:
0.00
AC:
0
AN:
43476
GnomAD4 genome
Cov.:
34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.73
CADD
Benign
1.3
DANN
Benign
0.57
PhyloP100
-2.9
PromoterAI
0.011
Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs11665282; hg19: chr18-33767479; API