NM_001358530.2(MOCS1):c.1468C>T (p.Arg490Trp) AND Sulfite oxidase deficiency due to molybdenum cofactor deficiency type A

Germline classification:: Conflicting classifications of pathogenicity (2 submissions)
Last evaluated:: Oct 17, 2022
Review status:: criteria provided, conflicting classifications

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000987691.6

Allele description [Variation Report for NM_001358530.2(MOCS1):c.1468C>T (p.Arg490Trp)]

NM_001358530.2(MOCS1):c.1468C>T (p.Arg490Trp)

Gene:

MOCS1:molybdenum cofactor synthesis 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p21.2

Genomic location:

Preferred name:

NM_001358530.2(MOCS1):c.1468C>T (p.Arg490Trp)

HGVS:

NC_000006.12:g.39906800G>A
NG_009297.1:g.32679C>T
NM_001075098.4:c.*325C>T
NM_001358529.2:c.1420C>T
NM_001358530.2:c.1468C>TMANE SELECT
NM_001358531.2:c.1207C>T
NM_001358533.2:c.*325C>T
NM_001358534.2:c.*325C>T
NM_005943.6:c.*325C>T
NP_001345458.1:p.Arg474Trp
NP_001345459.1:p.Arg490Trp
NP_001345460.1:p.Arg403Trp
NC_000006.11:g.39874576G>A
NR_033233.2:n.1338C>T

Protein change:

R403W

Links:

dbSNP: rs201889779

NCBI 1000 Genomes Browser:

rs201889779

Molecular consequence:

NM_001075098.4:c.*325C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001358533.2:c.*325C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001358534.2:c.*325C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_005943.6:c.*325C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001358529.2:c.1420C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001358530.2:c.1468C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001358531.2:c.1207C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_033233.2:n.1338C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Sulfite oxidase deficiency due to molybdenum cofactor deficiency type A
Synonyms:: Molybdenum cofactor deficiency, complementation group A; Molybdenum Cofactor Deficiency A
Identifiers:: MONDO: MONDO:0009643; MedGen: C1854988; Orphanet: 833; OMIM: 252150

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001137108	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Likely benign (May 28, 2019)	unknown	clinical testing	Citation Link,
SCV002154087	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 17, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001137108

Mendelics

criteria provided, single submitter

(Mendelics Assertion Criteria 2017)

Likely benign
(May 28, 2019)

unknown

clinical testing

Citation Link,

SCV002154087

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 17, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9..

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Mendelics, SCV001137108.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002154087.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 490 of the MOCS1 protein (p.Arg490Trp). This variant is present in population databases (rs201889779, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with MOCS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 802211). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jan 19, 2025

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