NM_203446.3(SYNJ1):c.3126del (p.Ser1043fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 12, 2021
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:: RCV001051902.8

Allele description [Variation Report for NM_203446.3(SYNJ1):c.3126del (p.Ser1043fs)]

NM_203446.3(SYNJ1):c.3126del (p.Ser1043fs)

Gene:

SYNJ1:synaptojanin 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

21q22.11

Genomic location:

Preferred name:

NM_203446.3(SYNJ1):c.3126del (p.Ser1043fs)

HGVS:

NC_000021.9:g.32646518del
NG_030017.2:g.86526del
NM_001160302.2:c.3122delC
NM_001160306.2:c.3111del
NM_003895.4:c.3239delC
NM_203446.3:c.3126delMANE SELECT
NP_001153774.1:p.Ser1043Alafs
NP_001153774.1:p.Ser1043fs
NP_001153778.1:p.Ser1038fs
NP_003886.3:p.Ser1082Alafs
NP_003886.3:p.Ser1082fs
NP_982271.3:p.Ser1043fs
NC_000021.8:g.34018824del
NC_000021.8:g.34018828del
NG_030017.1:g.86528del
NM_001160302.1:c.3126del
NM_003895.3:c.3243del

Protein change:

S1038fs

Links:

dbSNP: rs1230133310

NCBI 1000 Genomes Browser:

rs1230133310

Molecular consequence:

NM_001160302.2:c.3122delC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001160306.2:c.3111del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_003895.4:c.3239delC - frameshift variant - [Sequence Ontology: SO:0001589]
NM_203446.3:c.3126del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Early-onset Parkinson disease 20
Identifiers:: MONDO: MONDO:0014233; MedGen: C3809824; Orphanet: 391411; OMIM: 615530

Name:: Developmental and epileptic encephalopathy, 53
Synonyms:: Epileptic encephalopathy, early infantile, 53
Identifiers:: MONDO: MONDO:0033362; MedGen: C4479313; OMIM: 617389

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001216084	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 12, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 25316601, 27435091, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001216084

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 12, 2021)

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

Citations

PubMed

Homozygous nonsense mutation in SYNJ1 associated with intractable epilepsy and tau pathology.

Dyment DA, Smith AC, Humphreys P, Schwartzentruber J, Beaulieu CL; FORGE Canada Consortium, Bulman DE, Majewski J, Woulfe J, Michaud J, Boycott KM.

Neurobiol Aging. 2015 Feb;36(2):1222.e1-5. doi: 10.1016/j.neurobiolaging.2014.09.005. Epub 2014 Sep 6.

PubMed [citation]

PMID:: 25316601

Loss of SYNJ1 dual phosphatase activity leads to early onset refractory seizures and progressive neurological decline.

Hardies K, Cai Y, Jardel C, Jansen AC, Cao M, May P, Djémié T, Hachon Le Camus C, Keymolen K, Deconinck T, Bhambhani V, Long C, Sajan SA, Helbig KL; AR working group of the EuroEPINOMICS RES Consortium, Suls A, Balling R, Helbig I, De Jonghe P, Depienne C, De Camilli P, Weckhuysen S.

Brain. 2016 Sep;139(Pt 9):2420-30. doi: 10.1093/brain/aww180. Epub 2016 Jul 19.

PubMed [citation]

PMID:: 27435091
PMCID:: PMC4995362

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001216084.6

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with SYNJ1-related conditions. ClinVar contains an entry for this variant (Variation ID: 848199). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ser1082Alafs*111) in the SYNJ1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SYNJ1 are known to be pathogenic (PMID: 25316601, 27435091).

#	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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