5-53096944-C-T

Position:

• chr5-53096944-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004531.5(MOCS2):​c.*1658G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00363 in 152,334 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0036 (1 hom., cov: 33)
  • Exomes 𝑓: 0.083 (0 hom.)
• Consequence: MOCS2 NM_004531.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.701

Genes affected

MOCS2 (HGNC:7193): (molybdenum cofactor synthesis 2) Eukaryotic molybdoenzymes use a unique molybdenum cofactor (MoCo) consisting of a pterin, termed molybdopterin, and the catalytically active metal molybdenum. MoCo is synthesized from precursor Z by the heterodimeric enzyme molybdopterin synthase. The large and small subunits of molybdopterin synthase are both encoded from this gene by overlapping open reading frames. The proteins were initially thought to be encoded from a bicistronic transcript. They are now thought to be encoded from monocistronic transcripts. Alternatively spliced transcripts have been found for this locus that encode the large and small subunits. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MOCS2	NM_004531.5	c.*1658G>A		3_prime_UTR_variant	7/7	ENST00000396954.8	NP_004522.1
MOCS2	NM_176806.4	c.*2145G>A		3_prime_UTR_variant	7/7	ENST00000450852.8	NP_789776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MOCS2	ENST00000396954.8	c.*1658G>A		3_prime_UTR_variant	7/7	1	NM_004531.5	ENSP00000380157	P1
MOCS2	ENST00000450852.8	c.*2145G>A		3_prime_UTR_variant	7/7	1	NM_176806.4	ENSP00000411022
MOCS2	ENST00000361377.8	c.*1994G>A		3_prime_UTR_variant	6/6	4		ENSP00000355160

Frequencies

GnomAD3 genomes AF: 0.00363 AC: 552 AN: 152202 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000893

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00726

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00559

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.00451

Gnomad OTH AF: 0.00957

GnomAD4 exome AF: 0.0833 AC: 1 AN: 12 Hom.: 0 Cov.: 0 AF XY: 0.125 AC XY: 1 AN XY: 8

Gnomad4 AFR exome AF: 0.00

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00362 AC: 552 AN: 152322 Hom.: 1 Cov.: 33 AF XY: 0.00397 AC XY: 296 AN XY: 74494

Gnomad4 AFR AF: 0.000890

Gnomad4 AMR AF: 0.00725

Gnomad4 ASJ AF: 0.0115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00560

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.00451

Gnomad4 OTH AF: 0.00947

Alfa AF: 0.00562 Hom.: 6

Bravo AF: 0.00413

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.78
DANN	Benign	0.56

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12152954; hg19: chr5-52392774;