rs397518418

Variant names:

• chr6-39913351-CA-C
• rs397518418
• NM_001358530.2:c.722delT

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_001358530.2(MOCS1):​c.722delT​(p.Leu241ArgfsTer6) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MOCS1 NM_001358530.2 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 9.28
• Publications: 3 publications found

Genes affected

MOCS1 (HGNC:7190): (molybdenum cofactor synthesis 1) Molybdenum cofactor biosynthesis is a conserved pathway leading to the biological activation of molybdenum. The protein encoded by this gene is involved in this pathway. This gene was originally thought to produce a bicistronic mRNA with the potential to produce two proteins (MOCS1A and MOCS1B) from adjacent open reading frames. However, only the first open reading frame (MOCS1A) has been found to encode a protein from the putative bicistronic mRNA, whereas additional splice variants are likely to produce a fusion between the two open reading frames. This gene is defective in patients with molybdenum cofactor deficiency, type A. A related pseudogene has been identified on chromosome 16. [provided by RefSeq, Nov 2017]

MOCS1 Gene-Disease associations (from GenCC):

• sulfite oxidase deficiency due to molybdenum cofactor deficiency type A

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

ACMG classification

Our verdict: Pathogenic. The variant received 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 6-39913351-CA-C is Pathogenic according to our data. Variant chr6-39913351-CA-C is described in ClinVar as Pathogenic. ClinVar VariationId is 6117.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001358530.2. 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
	MOCS1	NM_001358530.2	MANE Select	c.722delT	p.Leu241ArgfsTer6	frameshift	Exon 6 of 11	NP_001345459.1	Q9NZB8-1
	MOCS1	NM_001358529.2		c.722delT	p.Leu241ArgfsTer6	frameshift	Exon 6 of 10	NP_001345458.1	Q9NZB8-2
	MOCS1	NM_001358531.2		c.461delT	p.Leu154ArgfsTer6	frameshift	Exon 5 of 10	NP_001345460.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOCS1	ENST00000340692.10	TSL:5 MANE Select	c.722delT	p.Leu241ArgfsTer6	frameshift	Exon 6 of 11	ENSP00000344794.5	Q9NZB8-1
	MOCS1	ENST00000373188.6	TSL:1	c.722delT	p.Leu241ArgfsTer6	frameshift	Exon 6 of 11	ENSP00000362284.2	Q9NZB8-5
	MOCS1	ENST00000373181.8	TSL:1	n.461delT		non_coding_transcript_exon	Exon 6 of 11	ENSP00000362277.4	Q9NZB8-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
2	-	-	Sulfite oxidase deficiency due to molybdenum cofactor deficiency type A (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.3
Mutation Taster		=0/200	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs397518418; hg19: chr6-39881095;