rs61746375

Variant names:

• chr6-39925766-G-A
• rs61746375
• NM_001358530.2:c.330C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001358530.2(MOCS1):​c.330C>T​(p.Leu110Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00478 in 1,612,810 control chromosomes in the GnomAD database, including 289 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (146 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (143 hom.)
• Consequence: MOCS1 NM_001358530.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -4.16
• Publications: 0 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 6-39925766-G-A is Benign according to our data. Variant chr6-39925766-G-A is described in ClinVar as Benign. ClinVar VariationId is 356668.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.16 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0787 is higher than 0.05.

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.330C>T	p.Leu110Leu	synonymous	Exon 3 of 11	NP_001345459.1	Q9NZB8-1
	MOCS1	NM_001358529.2		c.330C>T	p.Leu110Leu	synonymous	Exon 3 of 10	NP_001345458.1	Q9NZB8-2
	MOCS1	NM_001358531.2		c.69C>T	p.Leu23Leu	synonymous	Exon 2 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.330C>T	p.Leu110Leu	synonymous	Exon 3 of 11	ENSP00000344794.5	Q9NZB8-1
	MOCS1	ENST00000373188.6	TSL:1	c.330C>T	p.Leu110Leu	synonymous	Exon 3 of 11	ENSP00000362284.2	Q9NZB8-5
	MOCS1	ENST00000373181.8	TSL:1	n.69C>T		non_coding_transcript_exon	Exon 3 of 11	ENSP00000362277.4	Q9NZB8-4

Frequencies

GnomAD3 genomes AF: 0.0234 AC: 3561 AN: 152164 Hom.: 146 Cov.: 32

Gnomad AFR AF: 0.0812

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00661

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000705

Gnomad OTH AF: 0.0153

GnomAD2 exomes AF: 0.00636 AC: 1588 AN: 249862 AF XY: 0.00474

Gnomad AFR exome AF: 0.0796

Gnomad AMR exome AF: 0.00472

Gnomad ASJ exome AF: 0.00290

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000818

Gnomad OTH exome AF: 0.00328

GnomAD4 exome AF: 0.00285 AC: 4157 AN: 1460528 Hom.: 143 Cov.: 31 AF XY: 0.00251 AC XY: 1824 AN XY: 726540

African (AFR) AF: 0.0831 AC: 2782 AN: 33480

American (AMR) AF: 0.00550 AC: 246 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00260 AC: 68 AN: 26136

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39700

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52146

Middle Eastern (MID) AF: 0.00347 AC: 20 AN: 5766

European-Non Finnish (NFE) AF: 0.000612 AC: 681 AN: 1111962

Other (OTH) AF: 0.00566 AC: 342 AN: 60374

GnomAD4 genome AF: 0.0234 AC: 3559 AN: 152282 Hom.: 146 Cov.: 32 AF XY: 0.0223 AC XY: 1658 AN XY: 74458

African (AFR) AF: 0.0809 AC: 3362 AN: 41540

American (AMR) AF: 0.00660 AC: 101 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5172

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.000706 AC: 48 AN: 68032

Other (OTH) AF: 0.0151 AC: 32 AN: 2114

Alfa AF: 0.0108 Hom.: 57

Bravo AF: 0.0274

Asia WGS AF: 0.00346 AC: 13 AN: 3478

EpiCase AF: 0.00104

EpiControl AF: 0.00166

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Sulfite oxidase deficiency due to molybdenum cofactor deficiency type A (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.4
DANN	Benign	0.76
PhyloP100		-4.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs61746375; hg19: chr6-39893510;