NM_001080467.3(MYO5B):c.3538-1G>A AND Cholestasis, progressive familial intrahepatic, 10

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 20, 2022
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV002248425.1

Allele description [Variation Report for NM_001080467.3(MYO5B):c.3538-1G>A]

NM_001080467.3(MYO5B):c.3538-1G>A

Gene:

MYO5B:myosin VB [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

18q21.1

Genomic location:

Preferred name:

NM_001080467.3(MYO5B):c.3538-1G>A

HGVS:

NC_000018.10:g.49872233C>T
NG_012925.2:g.327849G>A
NM_001080467.3:c.3538-1G>AMANE SELECT
NC_000018.9:g.47398603C>T

Nucleotide change:

IVS26AS, G-A, -1

Links:

OMIM: 606540.0012; dbSNP: rs2144094082

NCBI 1000 Genomes Browser:

rs2144094082

Molecular consequence:

NM_001080467.3:c.3538-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:: Cholestasis, progressive familial intrahepatic, 10 (PFIC10)
Identifiers:: MONDO: MONDO:0030810; MedGen: C5676981; OMIM: 619868

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002520524	OMIM	no assertion criteria provided	Pathogenic (May 20, 2022)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 28027573, 33525641

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002520524

OMIM

no assertion criteria provided

Pathogenic
(May 20, 2022)

germline

literature only

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	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Defects in myosin VB are associated with a spectrum of previously undiagnosed low γ-glutamyltransferase cholestasis.

Qiu YL, Gong JY, Feng JY, Wang RX, Han J, Liu T, Lu Y, Li LT, Zhang MH, Sheps JA, Wang NL, Yan YY, Li JQ, Chen L, Borchers CH, Sipos B, Knisely AS, Ling V, Xing QH, Wang JS.

Hepatology. 2017 May;65(5):1655-1669. doi: 10.1002/hep.29020. Epub 2017 Mar 23. Erratum in: Hepatology. 2017 Nov;66(5):1708-1709. doi: 10.1002/hep.29552.

PubMed [citation]

PMID:: 28027573
PMCID:: PMC5413810

Congenital Diarrhea and Cholestatic Liver Disease: Phenotypic Spectrum Associated with MYO5B Mutations.

Aldrian D, Vogel GF, Frey TK, Ayyıldız Civan H, Aksu AÜ, Avitzur Y, Ramos Boluda E, Çakır M, Demir AM, Deppisch C, Duba HC, Düker G, Gerner P, Hertecant J, Hornová J, Kathemann S, Koeglmeier J, Koutroumpa A, Lanzersdorfer R, Lev-Tzion R, Lima R, Mansour S, et al.

J Clin Med. 2021 Jan 28;10(3). doi: 10.3390/jcm10030481.

PubMed [citation]

PMID:: 33525641
PMCID:: PMC7865828

Details of each submission

From OMIM, SCV002520524.1

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

Description

In 2 sibs (P1 and P2), born of Han Chinese parents, with progressive familial intrahepatic cholestasis-10 (PFIC10; 619868), Qiu et al. (2017) identified compound heterozygous mutations in the MYO5B gene that were predicted to disrupt splicing: a c.3538-1G-A transition (c.3538-1G-A, NM_001080467) in the coiled-coil domain, and a c.2414+5G-T transversion (606540.0013) in the IQ domain. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, were each inherited from an unaffected parent. Functional studies of the variants and studies of patient cells were not performed. The severity of the disease varied between the 2 sibs: 1 continued to have persistent cholestasis at age 7.5 years, whereas the other had transient cholestasis that resolved by age 4.4 years.

Aldrian et al. (2021) stated that both the c.3538-1G-A (intron 26) and the c.2414+5G-T (intron 19) mutations resulted in in-frame deletions of 22 and 9 residues, respectively.

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

Last Updated: Dec 24, 2023

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