NM_032237.5(POMK):c.419A>G (p.Tyr140Cys) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 21, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV003001869.3

Allele description [Variation Report for NM_032237.5(POMK):c.419A>G (p.Tyr140Cys)]

NM_032237.5(POMK):c.419A>G (p.Tyr140Cys)

Gene:

POMK:protein O-mannose kinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8p11.21

Genomic location:

Preferred name:

NM_032237.5(POMK):c.419A>G (p.Tyr140Cys)

HGVS:

NC_000008.11:g.43122243A>G
NG_033235.1:g.33738A>G
NM_001277971.2:c.419A>G
NM_032237.4:c.419A>G
NM_032237.5:c.419A>GMANE SELECT
NP_001264900.1:p.Tyr140Cys
NP_115613.1:p.Tyr140Cys
NC_000008.10:g.42977386A>G

Protein change:

Y140C

Molecular consequence:

NM_001277971.2:c.419A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_032237.5:c.419A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12 (MDDGA12)
Synonyms:: WALKER-WARBURG SYNDROME OR MUSCLE-EYE-BRAIN DISEASE, POMK-RELATED
Identifiers:: MONDO: MONDO:0014101; MedGen: C3808964; Orphanet: 899; OMIM: 615249

Name:: Limb-girdle muscular dystrophy due to POMK deficiency
Synonyms:: MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY, LIMB-GIRDLE, POMK-RELATED; Muscular dystrophy-dystroglycanopathy (limb-girdle), type c, 12
Identifiers:: MONDO: MONDO:0014489; MedGen: C4015184; Orphanet: 445110; OMIM: 616094

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Hymenophyllum hirsutum voucher J.-Y. Dubuisson HR-1999-6 ribulose-1,5-bisphospha...
Hymenophyllum hirsutum voucher J.-Y. Dubuisson HR-1999-6 ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit (rbcL) gene, partial cds; rbcL-accD intergenic spacer, complete sequence; and acetyl-CoA carboxylase beta subunit (accD) gene, partial cds; chloroplast
gi|57340847|gb|AY775450.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003293183	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 21, 2023)	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

SCV003293183

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 21, 2023)

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

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV003293183.2

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

Description

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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt POMK protein function. ClinVar contains an entry for this variant (Variation ID: 2080362). This variant has not been reported in the literature in individuals affected with POMK-related conditions. This variant is present in population databases (rs34750053, gnomAD 0.01%). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 140 of the POMK protein (p.Tyr140Cys).

#	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: Oct 20, 2024

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