NM_145064.3(STAC3):c.806C>T (p.Pro269Leu) AND Bailey-Bloch congenital myopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 5, 2022
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:: RCV000701165.6

Allele description [Variation Report for NM_145064.3(STAC3):c.806C>T (p.Pro269Leu)]

NM_145064.3(STAC3):c.806C>T (p.Pro269Leu)

Gene:

STAC3:SH3 and cysteine rich domain 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q13.3

Genomic location:

Preferred name:

NM_145064.3(STAC3):c.806C>T (p.Pro269Leu)

HGVS:

NC_000012.12:g.57244537G>A
NG_033835.1:g.11657C>T
NM_001286256.2:c.689C>T
NM_001286257.2:c.248C>T
NM_145064.3:c.806C>TMANE SELECT
NP_001273185.1:p.Pro230Leu
NP_001273186.1:p.Pro83Leu
NP_659501.1:p.Pro269Leu
NC_000012.11:g.57638320G>A
NM_145064.2:c.806C>T
NR_104422.2:n.502C>T

Protein change:

P230L

Links:

dbSNP: rs367590066

NCBI 1000 Genomes Browser:

rs367590066

Molecular consequence:

NM_001286256.2:c.689C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001286257.2:c.248C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_145064.3:c.806C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_104422.2:n.502C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Bailey-Bloch congenital myopathy (CMYO13)
Synonyms:: Native American myopathy; Congenital myopathy cleft palate and malignant hyperthermia; STAC3 disorder; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009722; MedGen: C1850625; Orphanet: 168572; OMIM: 255995

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000829951	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 5, 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

SCV000829951

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 5, 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

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, SCV000829951.5

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

Description

Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 578220). This variant has not been reported in the literature in individuals affected with STAC3-related conditions. This variant is present in population databases (rs367590066, gnomAD 0.02%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 269 of the STAC3 protein (p.Pro269Leu). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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: Sep 29, 2024

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