NM_133181.4(EPS8L3):c.22G>A (p.Ala8Thr) AND Hypotrichosis 5

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jul 29, 2020
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:: RCV001030441.2

Allele description [Variation Report for NM_133181.4(EPS8L3):c.22G>A (p.Ala8Thr)]

NM_133181.4(EPS8L3):c.22G>A (p.Ala8Thr)

Gene:

EPS8L3:EPS8 like 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p13.3

Genomic location:

Preferred name:

NM_133181.4(EPS8L3):c.22G>A (p.Ala8Thr)

HGVS:

NC_000001.11:g.109761728C>T
NM_001319952.2:c.-71-169G>A
NM_024526.4:c.22G>A
NM_133181.4:c.22G>AMANE SELECT
NM_139053.3:c.22G>A
NP_078802.2:p.Ala8Thr
NP_573444.2:p.Ala8Thr
NP_620641.1:p.Ala8Thr
NC_000001.10:g.110304350C>T
NM_024526.3:c.22G>A
NM_133181.3:c.22G>A

Protein change:

A8T; ALA8THR

Links:

OMIM: 614989.0001; dbSNP: rs1650987435

NCBI 1000 Genomes Browser:

rs1650987435

Molecular consequence:

NM_001319952.2:c.-71-169G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_024526.4:c.22G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133181.4:c.22G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_139053.3:c.22G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hypotrichosis 5 (HYPT5)
Synonyms:: MARIE UNNA HEREDITARY HYPOTRICHOSIS 2
Identifiers:: MONDO: MONDO:0013017; MedGen: C2748535; Orphanet: 444; OMIM: 612841

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001193450	OMIM	no assertion criteria provided	Pathogenic (Mar 30, 2020)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 15347323, 23099647
SCV001432971	SIB Swiss Institute of Bioinformatics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jul 29, 2020)	unknown	curation	PubMed (2) [See all records that cite these PMIDs] 23099647, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001193450

OMIM

no assertion criteria provided

Pathogenic
(Mar 30, 2020)

germline

literature only

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

SCV001432971

SIB Swiss Institute of Bioinformatics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jul 29, 2020)

unknown

curation

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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	curation

Citations

PubMed

Marie Unna hereditary hypotrichosis: report of a Chinese family and evidence for genetic heterogeneity.

Yan KL, He PP, Yang S, Li M, Yang Q, Ren YQ, Cui Y, Gao M, Xiao FL, Huang W, Zhang XJ.

Clin Exp Dermatol. 2004 Sep;29(5):460-3.

PubMed [citation]

PMID:: 15347323

Exome sequencing identified a missense mutation of EPS8L3 in Marie Unna hereditary hypotrichosis.

Zhang X, Guo BR, Cai LQ, Jiang T, Sun LD, Cui Y, Hu JC, Zhu J, Chen G, Tang XF, Sun GQ, Tang HY, Liu Y, Li M, Li QB, Cheng H, Gao M, Li P, Yang X, Zuo XB, Zheng XD, Wang PG, et al.

J Med Genet. 2012 Dec;49(12):727-30. doi: 10.1136/jmedgenet-2012-101134. Epub 2012 Oct 25.

PubMed [citation]

PMID:: 23099647
PMCID:: PMC3512347

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV001193450.1

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

Description

In 8 affected members of a large 4-generation Chinese family with the Marie Unna form of hypotrichosis mapping to chromosome 1 (HYPT5; 612841) originally described by Yan et al. (2004), Zhang et al. (2012) identified heterozygosity for a c.22G-A transition (c.22G-A, NM_024526.3) in exon 2 of the EPS8L3 gene, resulting in an ala8-to-thr (A8T) substitution at a conserved residue. The mutation was not found in 7 unaffected family members, 676 controls, or 781 patients with other diseases who were all unrelated and ethnically and geographically matched, or in public variant databases.

#	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

From SIB Swiss Institute of Bioinformatics, SCV001432971.1

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

Description

This variant is interpreted as a variant of uncertain significance for Hypotrichosis 5, autosomal dominant. The following ACMG Tag(s) were applied: Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium (PM2); Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (PP1); Multiple lines of computational evidence suggest no impact on gene or gene product (BP4).

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

Last Updated: Apr 23, 2022

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