rs7758412

Variant names:

• chr6-39905370-G-A
• rs7758412
• NM_001358530.2:c.*987C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001358530.2(MOCS1):​c.*987C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0263 in 462,778 control chromosomes in the GnomAD database, including 405 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.043 (294 hom., cov: 33)
  • Exomes 𝑓: 0.018 (111 hom.)
• Consequence: MOCS1 NM_001358530.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.56
• Publications: 5 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 6-39905370-G-A is Benign according to our data. Variant chr6-39905370-G-A is described in ClinVar as Benign. ClinVar VariationId is 356618.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.108 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.*987C>T		3_prime_UTR	Exon 11 of 11	NP_001345459.1	Q9NZB8-1
	MOCS1	NM_001358529.2		c.*987C>T		3_prime_UTR	Exon 10 of 10	NP_001345458.1	Q9NZB8-2
	MOCS1	NM_001358531.2		c.*987C>T		3_prime_UTR	Exon 10 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.*987C>T		3_prime_UTR	Exon 11 of 11	ENSP00000344794.5	Q9NZB8-1
	MOCS1	ENST00000373188.6	TSL:1	c.*1755C>T		3_prime_UTR	Exon 11 of 11	ENSP00000362284.2	Q9NZB8-5
	MOCS1	ENST00000373181.8	TSL:1	n.842-1108C>T		intron	N/A	ENSP00000362277.4	Q9NZB8-4

Frequencies

GnomAD3 genomes AF: 0.0428 AC: 6512 AN: 152108 Hom.: 295 Cov.: 33

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0257

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.0464

Gnomad SAS AF: 0.00954

Gnomad FIN AF: 0.00452

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0156

Gnomad OTH AF: 0.0382

GnomAD2 exomes AF: 0.0218 AC: 3110 AN: 142860 AF XY: 0.0209

Gnomad AFR exome AF: 0.119

Gnomad AMR exome AF: 0.0184

Gnomad ASJ exome AF: 0.0123

Gnomad EAS exome AF: 0.0465

Gnomad FIN exome AF: 0.00516

Gnomad NFE exome AF: 0.0168

Gnomad OTH exome AF: 0.0213

GnomAD4 exome AF: 0.0182 AC: 5647 AN: 310552 Hom.: 111 Cov.: 0 AF XY: 0.0167 AC XY: 2950 AN XY: 176346

African (AFR) AF: 0.112 AC: 966 AN: 8632

American (AMR) AF: 0.0178 AC: 487 AN: 27284

Ashkenazi Jewish (ASJ) AF: 0.0127 AC: 137 AN: 10790

East Asian (EAS) AF: 0.0501 AC: 461 AN: 9210

South Asian (SAS) AF: 0.00818 AC: 489 AN: 59744

European-Finnish (FIN) AF: 0.00509 AC: 96 AN: 18860

Middle Eastern (MID) AF: 0.0572 AC: 159 AN: 2778

European-Non Finnish (NFE) AF: 0.0157 AC: 2489 AN: 158980

Other (OTH) AF: 0.0254 AC: 363 AN: 14274

GnomAD4 genome AF: 0.0429 AC: 6524 AN: 152226 Hom.: 294 Cov.: 33 AF XY: 0.0415 AC XY: 3091 AN XY: 74436

African (AFR) AF: 0.111 AC: 4594 AN: 41512

American (AMR) AF: 0.0257 AC: 393 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0133 AC: 46 AN: 3468

East Asian (EAS) AF: 0.0463 AC: 239 AN: 5164

South Asian (SAS) AF: 0.00955 AC: 46 AN: 4818

European-Finnish (FIN) AF: 0.00452 AC: 48 AN: 10620

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0156 AC: 1064 AN: 68024

Other (OTH) AF: 0.0378 AC: 80 AN: 2114

Alfa AF: 0.0257 Hom.: 139

Bravo AF: 0.0480

Asia WGS AF: 0.0340 AC: 119 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.015
DANN	Benign	0.45
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs7758412; hg19: chr6-39873146; COSMIC: COSV107287869; COSMIC: COSV107287869;