5-53096944-C-T

Variant names:

• chr5-53096944-C-T
• rs12152954
• NM_004531.5:c.*1658G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

MOCS2 Gene-Disease associations (from GenCC):

• sulfite oxidase deficiency due to molybdenum cofactor deficiency type B

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004531.5. 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
	MOCS2	NM_004531.5	MANE Select	c.*1658G>A		3_prime_UTR	Exon 7 of 7	NP_004522.1	O96007
	MOCS2	NM_176806.4	MANE Plus Clinical	c.*2145G>A		3_prime_UTR	Exon 7 of 7	NP_789776.1	O96033

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOCS2	ENST00000396954.8	TSL:1 MANE Select	c.*1658G>A		3_prime_UTR	Exon 7 of 7	ENSP00000380157.3	O96007
	MOCS2	ENST00000450852.8	TSL:1 MANE Plus Clinical	c.*2145G>A		3_prime_UTR	Exon 7 of 7	ENSP00000411022.3	O96033
	MOCS2	ENST00000855414.1		c.*1658G>A		3_prime_UTR	Exon 6 of 6	ENSP00000525473.1

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

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.125 AC: 1 AN: 8

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.000890 AC: 37 AN: 41566

American (AMR) AF: 0.00725 AC: 111 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 40 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00560 AC: 27 AN: 4824

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10626

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00451 AC: 307 AN: 68030

Other (OTH) AF: 0.00947 AC: 20 AN: 2112

Alfa AF: 0.00538 Hom.: 6

Bravo AF: 0.00413

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.78
DANN	Benign	0.56
PhyloP100		-0.70
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs12152954; hg19: chr5-52392774;