NM_003900.5(SQSTM1):c.240C>G (p.Asp80Glu) AND Frontotemporal dementia and/or amyotrophic lateral sclerosis 3

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 22, 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:: RCV002250939.1

Allele description [Variation Report for NM_003900.5(SQSTM1):c.240C>G (p.Asp80Glu)]

NM_003900.5(SQSTM1):c.240C>G (p.Asp80Glu)

Gene:

SQSTM1:sequestosome 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q35.3

Genomic location:

Preferred name:

NM_003900.5(SQSTM1):c.240C>G (p.Asp80Glu)

HGVS:

NC_000005.10:g.179822992C>G
NG_011342.1:g.21605C>G
NM_001142298.2:c.-13C>G
NM_001142299.2:c.-13C>G
NM_003900.5:c.240C>GMANE SELECT
NP_003891.1:p.Asp80Glu
NC_000005.9:g.179249992C>G

Protein change:

D80E

Links:

dbSNP: rs148366738

NCBI 1000 Genomes Browser:

rs148366738

Molecular consequence:

NM_001142298.2:c.-13C>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001142299.2:c.-13C>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_003900.5:c.240C>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Frontotemporal dementia and/or amyotrophic lateral sclerosis 3
Synonyms:: FTDALS3
Identifiers:: MONDO: MONDO:0014640; MedGen: C4225326; Orphanet: 275864; Orphanet: 275872; Orphanet: 803; OMIM: 616437

Recent activity

Clear Turn Off Turn On

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
SCV002521172	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (May 22, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24899140, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002521172

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(May 22, 2022)

germline

clinical testing

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	yes	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

Rare mutations in SQSTM1 modify susceptibility to frontotemporal lobar degeneration.

van der Zee J, Van Langenhove T, Kovacs GG, Dillen L, Deschamps W, Engelborghs S, Matěj R, Vandenbulcke M, Sieben A, Dermaut B, Smets K, Van Damme P, Merlin C, Laureys A, Van Den Broeck M, Mattheijssens M, Peeters K, Benussi L, Binetti G, Ghidoni R, Borroni B, Padovani A, et al.

Acta Neuropathol. 2014 Sep;128(3):397-410. doi: 10.1007/s00401-014-1298-7. Epub 2014 Jun 5.

PubMed [citation]

PMID:: 24899140
PMCID:: PMC4131163

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From 3billion, SCV002521172.1

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

Description

The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: <0.001%). Protein truncation variants are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.76; 3Cnet: 0.01). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with SQSTM1 related disorder (PMID: 24899140). However, the evidence of pathogenicity is insufficient at this time. Therefore, this variant is classified as uncertain significanceaccording 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

Last Updated: Dec 24, 2023

ClinVar

Relating variation to medicine