NM_032237.5(POMK):c.965C>T (p.Pro322Leu) AND Limb-girdle muscular dystrophy due to POMK deficiency

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 3, 2018
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:: RCV001004956.2

Allele description [Variation Report for NM_032237.5(POMK):c.965C>T (p.Pro322Leu)]

NM_032237.5(POMK):c.965C>T (p.Pro322Leu)

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.965C>T (p.Pro322Leu)

HGVS:

NC_000008.11:g.43122789C>T
NG_033235.1:g.34284C>T
NM_001277971.2:c.965C>T
NM_032237.5:c.965C>TMANE SELECT
NP_001264900.1:p.Pro322Leu
NP_115613.1:p.Pro322Leu
NC_000008.10:g.42977932C>T
p.Pro322Leu

Protein change:

P322L

Links:

dbSNP: rs747083630

NCBI 1000 Genomes Browser:

rs747083630

Molecular consequence:

NM_001277971.2:c.965C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_032237.5:c.965C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

Recent activity

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organic cation/carnitine transporter 4-like [Cucurbita maxima]
organic cation/carnitine transporter 4-like [Cucurbita maxima]
gi|1280995532|ref|XP_022981446.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001164488	Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Dec 3, 2018)	germline	research	PubMed (2) [See all records that cite these PMIDs] 29910097, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001164488

Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Dec 3, 2018)

germline

research

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	research

Citations

PubMed

A novel compound heterozygous mutation in the POMK gene causing limb-girdle muscular dystrophy-dystroglycanopathy in a sib pair.

Strang-Karlsson S, Johnson K, Töpf A, Xu L, Lek M, MacArthur DG, Casar-Borota O, Williams M, Straub V, Wallgren-Pettersson C.

Neuromuscul Disord. 2018 Jul;28(7):614-618. doi: 10.1016/j.nmd.2018.04.012. Epub 2018 May 16.

PubMed [citation]

PMID:: 29910097
PMCID:: PMC9429833

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, SCV001164488.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (2)

Description

The heterozygous p.Pro322Leu variant in POMK was identified by our study in the compound heterozygous state, with a VUS, in two siblings with limb-girdle muscular dystrophy (LGMD) (PMID: 29910097). This variant has been identified in 0.0008959% (1/111624) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs747083630). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Pro322Leu variant is uncertain. ACMG/AMP Criteria applied: PM2, PM3 (Richards 2015).

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

Last Updated: Mar 30, 2024

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