NM_014363.6(SACS):c.5743_5744del (p.His1915fs) AND Spastic paraplegia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 23, 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:: RCV001951390.6

Allele description [Variation Report for NM_014363.6(SACS):c.5743_5744del (p.His1915fs)]

NM_014363.6(SACS):c.5743_5744del (p.His1915fs)

Gene:

SACS:sacsin molecular chaperone [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

13q12.12

Genomic location:

Preferred name:

NM_014363.6(SACS):c.5743_5744del (p.His1915fs)

HGVS:

NC_000013.11:g.23338133_23338134del
NG_012342.1:g.100570_100571del
NM_001278055.2:c.5302_5303del
NM_014363.6:c.5743_5744delMANE SELECT
NP_001264984.1:p.His1768fs
NP_055178.3:p.His1915fs
NC_000013.10:g.23912271_23912272del
NC_000013.10:g.23912272_23912273del

Protein change:

H1768fs

Links:

dbSNP: rs2137616213

NCBI 1000 Genomes Browser:

rs2137616213

Molecular consequence:

NM_001278055.2:c.5302_5303del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_014363.6:c.5743_5744del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Spastic paraplegia
Identifiers:: MedGen: C0037772; Human Phenotype Ontology: HP:0001258

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HOXB5 homeobox B5 [Homo sapiens]
HOXB5 homeobox B5 [Homo sapiens]
Gene ID:3215

Gene
Gene Links for GEO Profiles (Select 108356548) (1)
Gene
Chromosome neighbors for GEO Profiles (Select 108381498) (20)
GEO Profiles
Related DataSets for GEO Profiles (Select 108387642) (1)
GEO DataSets
Telomere-elongated, prostate cancer cells
Telomere-elongated, prostate cancer cells
Accession: GDS4964

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002246672	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 23, 2022)	germline	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

SCV002246672

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 23, 2022)

germline

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

Citations

PubMed

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, SCV002246672.3

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the SACS protein in which other variant(s) (p.Tyr4538*) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 1460037). This variant has not been reported in the literature in individuals affected with SACS-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.His1915Cysfs*19) in the SACS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 2665 amino acid(s) of the SACS protein.

#	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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