5-53095702-T-C

Position:

• chr5-53095702-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_004531.5(MOCS2):​c.*2900A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0149 in 152,154 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (22 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MOCS2 NM_004531.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.446

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 5-53095702-T-C is Benign according to our data. Variant chr5-53095702-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 907140.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0149 (2274/152154) while in subpopulation NFE AF= 0.0225 (1530/67988). AF 95% confidence interval is 0.0216. There are 22 homozygotes in gnomad4. There are 1080 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MOCS2	NM_004531.5	c.*2900A>G		3_prime_UTR_variant	7/7	ENST00000396954.8	NP_004522.1
MOCS2	NM_176806.4	c.*3387A>G		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.*2900A>G		3_prime_UTR_variant	7/7	1	NM_004531.5	ENSP00000380157	P1
MOCS2	ENST00000450852.8	c.*3387A>G		3_prime_UTR_variant	7/7	1	NM_176806.4	ENSP00000411022
MOCS2	ENST00000361377.8	c.*3236A>G		3_prime_UTR_variant	6/6	4		ENSP00000355160

Frequencies

GnomAD3 genomes AF: 0.0150 AC: 2274 AN: 152034 Hom.: 22 Cov.: 32

Gnomad AFR AF: 0.00401

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0156

Gnomad ASJ AF: 0.0210

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00477

Gnomad FIN AF: 0.0178

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0225

Gnomad OTH AF: 0.0186

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0149 AC: 2274 AN: 152154 Hom.: 22 Cov.: 32 AF XY: 0.0145 AC XY: 1080 AN XY: 74404

Gnomad4 AFR AF: 0.00402

Gnomad4 AMR AF: 0.0155

Gnomad4 ASJ AF: 0.0210

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00477

Gnomad4 FIN AF: 0.0178

Gnomad4 NFE AF: 0.0225

Gnomad4 OTH AF: 0.0184

Alfa AF: 0.00822 Hom.: 2

Bravo AF: 0.0156

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

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

Likely benign, 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.9
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs116368818; hg19: chr5-52391532;