NM_005639.3(SYT1):c.908T>A (p.Met303Lys) AND Infantile hypotonia-oculomotor anomalies-hyperkinetic movements-developmental delay syndrome

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Feb 18, 2019
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:: RCV000735271.2

Allele description [Variation Report for NM_005639.3(SYT1):c.908T>A (p.Met303Lys)]

NM_005639.3(SYT1):c.908T>A (p.Met303Lys)

Gene:

SYT1:synaptotagmin 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q21.2

Genomic location:

Preferred name:

NM_005639.3(SYT1):c.908T>A (p.Met303Lys)

HGVS:

NC_000012.12:g.79353599T>A
NM_001135805.2:c.908T>A
NM_001135806.2:c.908T>A
NM_001291901.2:c.899T>A
NM_005639.3:c.908T>AMANE SELECT
NP_001129277.1:p.Met303Lys
NP_001129278.1:p.Met303Lys
NP_001278830.1:p.Met300Lys
NP_005630.1:p.Met303Lys
NC_000012.11:g.79747379T>A
NM_005639.2:c.908T>A

Protein change:

M300K; MET303LYS

Links:

OMIM: 185605.0004; dbSNP: rs1565922388

NCBI 1000 Genomes Browser:

rs1565922388

Molecular consequence:

NM_001135805.2:c.908T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001135806.2:c.908T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001291901.2:c.899T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_005639.3:c.908T>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Infantile hypotonia-oculomotor anomalies-hyperkinetic movements-developmental delay syndrome
Synonyms:: BAKER-GORDON SYNDROME; NEURODEVELOPMENTAL DISORDER WITH INVOLUNTARY MOVEMENT AND ABNORMAL ELECTROENCEPHALOGRAM
Identifiers:: MONDO: MONDO:0033864; MedGen: C4748715; OMIM: 618218

Recent activity

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conserved hypothetical protein [Streptomyces scabiei 87.22]
conserved hypothetical protein [Streptomyces scabiei 87.22]
gi|260644160|emb|CBG67233.1|

Protein
Symphodus melanocercus isolate LB168 cytochrome oxidase subunit I (COI) gene, pa...
Symphodus melanocercus isolate LB168 cytochrome oxidase subunit I (COI) gene, partial cds; mitochondrial
gi|257218543|gb|GQ341600.1|

Nucleotide
Centrolabrus exoletus isolate 1 pop-variant continental Portugal 16S ribosomal R...
Centrolabrus exoletus isolate 1 pop-variant continental Portugal 16S ribosomal RNA gene, partial sequence; mitochondrial gene for mitochondrial product
gi|20278667|gb|AY092041.1|

Nucleotide
Symphodus bailloni isolate LB245 cytochrome oxidase subunit I (COI) gene, partia...
Symphodus bailloni isolate LB245 cytochrome oxidase subunit I (COI) gene, partial cds; mitochondrial
gi|257218545|gb|GQ341601.1|

Nucleotide
Symphodus melops isolate 1 pop-variant continental Portugal 16S ribosomal RNA ge...
Symphodus melops isolate 1 pop-variant continental Portugal 16S ribosomal RNA gene, partial sequence; mitochondrial gene for mitochondrial product
gi|20278664|gb|AY092038.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000863519	OMIM	no assertion criteria provided	Pathogenic (Dec 12, 2018)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 30107533, 25712080
SCV000994931	SIB Swiss Institute of Bioinformatics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Feb 18, 2019)	unknown	curation	PubMed (3) [See all records that cite these PMIDs] 25712080, 30107533, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000863519

OMIM

no assertion criteria provided

Pathogenic
(Dec 12, 2018)

germline

literature only

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

SCV000994931

SIB Swiss Institute of Bioinformatics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Feb 18, 2019)

unknown

curation

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	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	curation

Citations

PubMed

Novel de novo heterozygous loss-of-function variants in MED13L and further delineation of the MED13L haploinsufficiency syndrome.

Cafiero C, Marangi G, Orteschi D, Ali M, Asaro A, Ponzi E, Moncada A, Ricciardi S, Murdolo M, Mancano G, Contaldo I, Leuzzi V, Battaglia D, Mercuri E, Slavotinek AM, Zollino M.

Eur J Hum Genet. 2015 Nov;23(11):1499-504. doi: 10.1038/ejhg.2015.19. Epub 2015 Feb 25.

PubMed [citation]

PMID:: 25712080
PMCID:: PMC4613466

SYT1-associated neurodevelopmental disorder: a case series.

Baker K, Gordon SL, Melland H, Bumbak F, Scott DJ, Jiang TJ, Owen D, Turner BJ, Boyd SG, Rossi M, Al-Raqad M, Elpeleg O, Peck D, Mancini GMS, Wilke M, Zollino M, Marangi G, Weigand H, Borggraefe I, Haack T, Stark Z, Sadedin S; et al.

Brain. 2018 Sep 1;141(9):2576-2591. doi: 10.1093/brain/awy209.

PubMed [citation]

PMID:: 30107533
PMCID:: PMC6113648

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000863519.1

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

Description

In a 7-year-old patient (patient 6) with Baker-Gordon syndrome (BAGOS; 618218), Baker et al. (2018) identified a de novo heterozygous c.908T-A transversion in the SYT1 gene, resulting in a met303-to-lys (M303K) substitution at a highly conserved residue in the C2B calcium-binding domain. This patient had originally been reported by Cafiero et al. (2015) (patient 4). The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not present in the gnomAD database. Transfection of the mutation into rodent hippocampal neurons showed that the M303K variant was expressed at lower levels compared to wildtype and also failed to localize at nerve terminals.

#	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 SIB Swiss Institute of Bioinformatics, SCV000994931.1

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

Description

This variant is interpreted as a Likely pathogenic for Baker-Gordon syndrome, autosomal dominant. The following ACMG Tag(s) were applied: PM2: Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PM6: Assumed de novo, but without confirmation of paternity and maternity. PS3-Moderate: Well-established functional studies show a deleterious effect (downgraded to Moderate). PM1: Located in a mutational hot spot and/or critical and well-established functional domain (e.g., active site of an enzyme) without benign variation.

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

Last Updated: Apr 23, 2022

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