NM_139248.3(LIPH):c.736T>A (p.Cys246Ser) AND Hypotrichosis 7

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Apr 22, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000490454.4

Allele description [Variation Report for NM_139248.3(LIPH):c.736T>A (p.Cys246Ser)]

NM_139248.3(LIPH):c.736T>A (p.Cys246Ser)

Gene:

LIPH:lipase H [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3q27.2

Genomic location:

Preferred name:

NM_139248.3(LIPH):c.736T>A (p.Cys246Ser)

HGVS:

NC_000003.12:g.185519292A>T
NG_012183.1:g.38290T>A
NM_139248.3:c.736T>AMANE SELECT
NP_640341.1:p.Cys246Ser
NC_000003.11:g.185237080A>T
NM_139248.2:c.736T>A
p.Cys246Ser

Protein change:

C246S; CYS246SER

Links:

OMIM: 607365.0007; dbSNP: rs201249971

NCBI 1000 Genomes Browser:

rs201249971

Molecular consequence:

NM_139248.3:c.736T>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Hypotrichosis 7 (HYPT7)
Synonyms:: HYPOTRICHOSIS, LOCALIZED, AUTOSOMAL RECESSIVE 2; HYPOTRICHOSIS, AUTOSOMAL RECESSIVE; Total Hypotrichosis, Mari type; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011452; MedGen: C1836672; Orphanet: 55654; OMIM: 604379

Recent activity

Clear Turn Off Turn On

Astarte castanea cytochrome oxidase 1 (COI) gene, partial cds; mitochondrial gen...
Astarte castanea cytochrome oxidase 1 (COI) gene, partial cds; mitochondrial gene for mitochondrial product
gi|18026505|gb|AF120662.1|

Nucleotide
Sepia officinalis isolate SOIM1H cytochrome c oxidase subunit I gene, partial cd...
Sepia officinalis isolate SOIM1H cytochrome c oxidase subunit I gene, partial cds; mitochondrial
gi|1761173804|gb|MN069250.1|

Nucleotide
Sepia officinalis isolate SOPP1H cytochrome c oxidase subunit I gene, partial cd...
Sepia officinalis isolate SOPP1H cytochrome c oxidase subunit I gene, partial cds; mitochondrial
gi|1761173802|gb|MN069249.1|

Nucleotide
TET16 tetraspanin [Arabidopsis thaliana]
TET16 tetraspanin [Arabidopsis thaliana]
Gene ID:838432

Gene

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000267385	Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 18, 2016)	germline	reference population	PubMed (4) [See all records that cite these PMIDs] 19892526, 24722066, 23590372, 25741868
SCV002318632	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 22, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 19892526, 25741868
SCV002503834	Molecular Genetics, Royal Melbourne Hospital See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 22, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 19892526, 20213768, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000267385

Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Mar 18, 2016)

germline

reference population

PubMed (4)
[See all records that cite these PMIDs]

SCV002318632

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Mar 22, 2022)

germline

clinical testing

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

SCV002503834

Molecular Genetics, Royal Melbourne Hospital

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Apr 22, 2022)

germline

clinical testing

PubMed (3)
[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	1	not provided	not provided	1	not provided	clinical testing
East Asian	germline	unknown	1	not provided	not provided	not provided	not provided	reference population

Citations

PubMed

A homozygous mutation, c.736T>A (p.C246S), in LIPH gene in a patient manifesting woolly hair, hypotrichosis, hearing difficulty, cleft palate and amblyopia.

Hamada K, Kubo R, Nishio D, Nakamura M.

Eur J Dermatol. 2014 Mar-Apr;24(2):272-3. doi: 10.1684/ejd.2014.2306. No abstract available.

PubMed [citation]

PMID:: 24722066

Two cases of autosomal recessive woolly hair with LIPH gene mutations.

Harada K, Inozume T, Kawamura T, Shibagaki N, Kinoshita T, Deguchi N, Shimada S.

Int J Dermatol. 2013 May;52(5):572-4. doi: 10.1111/j.1365-4632.2012.05775.x.

PubMed [citation]

PMID:: 23590372

See all PubMed Citations (5)

Details of each submission

From Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center, SCV000267385.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	East Asian	1	not provided	not provided	reference population	PubMed (4)

#	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		1	not provided	not provided	not provided

From 3billion, SCV002318632.1

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

Description

Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000225403, PMID:19892526). In silico tool predictions suggest damaging effect of the variant on gene or gene product(REVEL: 0.956>=0.6). A missense variant is a common mechanism . The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.0001552). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.

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

From Molecular Genetics, Royal Melbourne Hospital, SCV002503834.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change is predicted to replace cysteine with serine at codon 246 of the LIPH protein, p.(Cys246Ser). The cysteine residue is invariant across species (100 vertebrates, UCSC), and forms a crucial disulphide bond in the lipase domain. There is a large physicochemical difference between cysteine and serine. The variant is present in a large population cohort at a frequency of 0.016% (rs201249971, 39/251,346 alleles, 0 homozygotes in gnomAD v2.1), with a frequency of 0.15% in the East Asian population (36/18,394 alleles). The variant is a Japanese founder variant that has been identified in the homozygous state and compound heterozygous with a second pathogenic allele in multiple individuals with autosomal recessive woolly hair/hypotrichosis, and segregates with disease in at least one family (PMID: 19892526, 20213768). Additionally, in vitro functional assays show complete abolition of hydrolytic activity and no ability to activate P2Y5 for the variant (PMID: 20213768). Multiple lines of computational evidence predict a deleterious effect for the missense substitution (6/6 algorithms). Based on the classification scheme RMH Modified ACMG Guidelines v1.3.0, this variant is classified as PATHOGENIC. Following criteria are met: PM3_VeryStrong, PM1, PS3_Supporting, PP1, PP3.

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine