NM_001358530.2:c.*987C>T

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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, ClinGen

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MOCS1	NM_001358530.2	c.*987C>T		3_prime_UTR_variant	Exon 11 of 11	ENST00000340692.10	NP_001345459.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MOCS1	ENST00000340692.10	c.*987C>T		3_prime_UTR_variant	Exon 11 of 11	5	NM_001358530.2	ENSP00000344794.5

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

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

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;