rs149639104

Variant names:

• chr18-36199692-G-A
• rs149639104
• NM_017947.4:c.309G>A

Your query was ambiguous. Multiple possible variants found:

• chr18-36199692-G-A
• chr18-36199692-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_017947.4(MOCOS):​c.309G>A​(p.Ala103Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00584 in 1,613,594 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0042 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0060 (58 hom.)
• Consequence: MOCOS NM_017947.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.817
• 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]

MOCOS Gene-Disease associations (from GenCC):

• xanthinuria type II

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 18-36199692-G-A is Benign according to our data. Variant chr18-36199692-G-A is described in ClinVar as Benign. ClinVar VariationId is 536216.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.817 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00424 (646/152224) while in subpopulation SAS AF = 0.0154 (74/4814). AF 95% confidence interval is 0.0126. There are 3 homozygotes in GnomAd4. There are 324 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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.309G>A	p.Ala103Ala	synonymous	Exon 4 of 15	NP_060417.4	Q96EN8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOCOS	ENST00000261326.6	TSL:1 MANE Select	c.309G>A	p.Ala103Ala	synonymous	Exon 4 of 15	ENSP00000261326.4	Q96EN8
	MOCOS	ENST00000880903.1		c.309G>A	p.Ala103Ala	synonymous	Exon 4 of 16	ENSP00000550962.1
	MOCOS	ENST00000880908.1		c.219G>A	p.Ala73Ala	synonymous	Exon 3 of 14	ENSP00000550967.1

Frequencies

GnomAD3 genomes AF: 0.00425 AC: 647 AN: 152106 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00133

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00386

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0156

Gnomad FIN AF: 0.00434

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00560

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00613 AC: 1538 AN: 250994 AF XY: 0.00715

Gnomad AFR exome AF: 0.000862

Gnomad AMR exome AF: 0.00136

Gnomad ASJ exome AF: 0.00526

Gnomad EAS exome AF: 0.000218

Gnomad FIN exome AF: 0.00574

Gnomad NFE exome AF: 0.00595

Gnomad OTH exome AF: 0.00653

GnomAD4 exome AF: 0.00601 AC: 8780 AN: 1461370 Hom.: 58 Cov.: 31 AF XY: 0.00643 AC XY: 4676 AN XY: 727018

African (AFR) AF: 0.000837 AC: 28 AN: 33456

American (AMR) AF: 0.00165 AC: 74 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00471 AC: 123 AN: 26136

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39700

South Asian (SAS) AF: 0.0194 AC: 1675 AN: 86236

European-Finnish (FIN) AF: 0.00510 AC: 272 AN: 53356

Middle Eastern (MID) AF: 0.0104 AC: 56 AN: 5400

European-Non Finnish (NFE) AF: 0.00557 AC: 6189 AN: 1112008

Other (OTH) AF: 0.00592 AC: 357 AN: 60354

GnomAD4 genome AF: 0.00424 AC: 646 AN: 152224 Hom.: 3 Cov.: 33 AF XY: 0.00435 AC XY: 324 AN XY: 74440

African (AFR) AF: 0.00132 AC: 55 AN: 41528

American (AMR) AF: 0.00386 AC: 59 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00548 AC: 19 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.0154 AC: 74 AN: 4814

European-Finnish (FIN) AF: 0.00434 AC: 46 AN: 10610

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00560 AC: 381 AN: 68014

Other (OTH) AF: 0.00426 AC: 9 AN: 2114

Alfa AF: 0.00498 Hom.: 1

Bravo AF: 0.00368

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.00562

EpiControl AF: 0.00545

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Xanthinuria type II (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.39
DANN	Benign	0.45
PhyloP100		-0.82
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs149639104; hg19: chr18-33779655; COSMIC: COSV54342307;