NM_152393.4(KLHL40):c.275C>G (p.Ser92Ter) AND Nemaline myopathy 8

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 25, 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:: RCV002750173.3

Allele description [Variation Report for NM_152393.4(KLHL40):c.275C>G (p.Ser92Ter)]

NM_152393.4(KLHL40):c.275C>G (p.Ser92Ter)

Gene:

KLHL40:kelch like family member 40 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p22.1

Genomic location:

Preferred name:

NM_152393.4(KLHL40):c.275C>G (p.Ser92Ter)

HGVS:

NC_000003.12:g.42685893C>G
NG_033035.1:g.5375C>G
NM_152393.4:c.275C>GMANE SELECT
NP_689606.2:p.Ser92Ter
NC_000003.11:g.42727385C>G

Protein change:

S92*

Molecular consequence:

NM_152393.4:c.275C>G - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Nemaline myopathy 8 (NEM8)
Synonyms:: Nemaline myopathy 8, autosomal recessive
Identifiers:: MONDO: MONDO:0014138; MedGen: C3809209; Orphanet: 171430; OMIM: 615348

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003013447	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 25, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23746549, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003013447

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 25, 2022)

germline

clinical testing

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in KLHL40 are a frequent cause of severe autosomal-recessive nemaline myopathy.

Ravenscroft G, Miyatake S, Lehtokari VL, Todd EJ, Vornanen P, Yau KS, Hayashi YK, Miyake N, Tsurusaki Y, Doi H, Saitsu H, Osaka H, Yamashita S, Ohya T, Sakamoto Y, Koshimizu E, Imamura S, Yamashita M, Ogata K, Shiina M, Bryson-Richardson RJ, Vaz R, et al.

Am J Hum Genet. 2013 Jul 11;93(1):6-18. doi: 10.1016/j.ajhg.2013.05.004. Epub 2013 Jun 6.

PubMed [citation]

PMID:: 23746549
PMCID:: PMC3710748

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, SCV003013447.2

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

Description

This sequence change creates a premature translational stop signal (p.Ser92*) in the KLHL40 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in KLHL40 are known to be pathogenic (PMID: 23746549). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with KLHL40-related conditions. This variant is present in population databases (no rsID available, gnomAD no frequency).

#	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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