NM_004820.5(CYP7B1):c.1162C>T (p.Arg388Ter) AND Hereditary spastic paraplegia 5A

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Feb 27, 2020
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:: RCV000006474.7

Allele description

NM_004820.5(CYP7B1):c.1162C>T (p.Arg388Ter)

Gene:

CYP7B1:cytochrome P450 family 7 subfamily B member 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8q12.3

Genomic location:

Preferred name:

NM_004820.5(CYP7B1):c.1162C>T (p.Arg388Ter)

HGVS:

NC_000008.11:g.64604753G>A
NG_008338.2:g.199039C>T
NM_001324112.2:c.1162C>T
NM_004820.5:c.1162C>TMANE SELECT
NP_001311041.1:p.Arg388Ter
NP_004811.1:p.Arg388Ter
NC_000008.10:g.65517310G>A
NM_004820.3:c.1162C>T

Protein change:

R388*; ARG388TER

Links:

OMIM: 603711.0001; dbSNP: rs72554620

NCBI 1000 Genomes Browser:

rs72554620

Molecular consequence:

NM_001324112.2:c.1162C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_004820.5:c.1162C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Name:: Hereditary spastic paraplegia 5A (SPG5A)
Synonyms:: SPASTIC PARAPLEGIA 5A, AUTOSOMAL RECESSIVE; Spastic paraplegia 5A; Autosomal recessive spastic paraplegia
Identifiers:: MONDO: MONDO:0010047; MedGen: C1849115; Orphanet: 100986; OMIM: 270800

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000026657	OMIM	no assertion criteria provided	Pathogenic (Feb 1, 2008)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 18252231, 9802883
SCV001367373	Centre for Mendelian Genomics, University Medical Centre Ljubljana	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 27, 2020)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001451298	Paris Brain Institute, Inserm - ICM	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	unknown	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

SCV000026657

OMIM

no assertion criteria provided

Pathogenic
(Feb 1, 2008)

germline

literature only

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

SCV001367373

Centre for Mendelian Genomics, University Medical Centre Ljubljana

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Feb 27, 2020)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001451298

Paris Brain Institute, Inserm - ICM

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

unknown

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	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	unknown	yes	2	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sequence alterations within CYP7B1 implicate defective cholesterol homeostasis in motor-neuron degeneration.

Tsaousidou MK, Ouahchi K, Warner TT, Yang Y, Simpson MA, Laing NG, Wilkinson PA, Madrid RE, Patel H, Hentati F, Patton MA, Hentati A, Lamont PJ, Siddique T, Crosby AH.

Am J Hum Genet. 2008 Feb;82(2):510-5. doi: 10.1016/j.ajhg.2007.10.001. Epub 2008 Jan 18.

PubMed [citation]

PMID:: 18252231
PMCID:: PMC2426914

Identification of a new inborn error in bile acid synthesis: mutation of the oxysterol 7alpha-hydroxylase gene causes severe neonatal liver disease.

Setchell KD, Schwarz M, O'Connell NC, Lund EG, Davis DL, Lathe R, Thompson HR, Weslie Tyson R, Sokol RJ, Russell DW.

J Clin Invest. 1998 Nov 1;102(9):1690-703.

PubMed [citation]

PMID:: 9802883
PMCID:: PMC509117

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000026657.3

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

Description

Congenital Bile Acid Synthesis Defect 3

In a 10-week-old boy with a metabolic defect in bile acid synthesis involving a deficiency in 7-alpha-hydroxylation (CBAS3; 613812), Setchell et al. (1998) identified a homozygous C-to-T transition in the CYP7B1 gene, resulting in an arg388-to-ter (R388X) substitution.

Spastic Paraplegia 5A

In a patient with sporadic spastic paraplegia-5A (SPG5A; 270800), Tsaousidou et al. (2008) identified a homozygous 1162C-T transition in the CYP7B1 gene, resulting in an R388X substitution. The patient had symptoms of pure motor neuron degeneration without other features. Tsaousidou et al. (2008) postulated that the patient reported by Setchell et al. (1998) may have had loss of both alpha-hydroxylating enzymes, CYP7B1 and CYP7A1 (118455), to result in such a severe phenotype.

#	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 Centre for Mendelian Genomics, University Medical Centre Ljubljana, SCV001367373.2

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

Description

This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PS4_MOD,PM2.

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

From Paris Brain Institute, Inserm - ICM, SCV001451298.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		2	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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