SYT14

protein-coding

synaptotagmin 14, the group of Synaptotagmins

Gene summary

This gene is a member of the synaptotagmin gene family and encodes a protein similar to other family members that mediate membrane trafficking in synaptic transmission. The encoded protein is a calcium-independent synaptotagmin. Mutations in this gene are a cause of autosomal recessive spinocerebellar ataxia-11 (SCAR11), and a t(1;3) translocation of this gene has been associated with neurodevelopmental abnormalities. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 4. [provided by RefSeq, Dec 2011]

MANE transcript

NM_001146262.4

Inheritance

ClinVar variants

P:2U:78B:21

Top phenotype

Spinocerebellar ataxia, autosomal recessive 11

gnomAD constraint

pLI —, LoF o/e 0.15

Max pathogenic AF

—

Genomic locus

chr1:209,900,923-210,171,389

External References & Databases

Ensembl (ENSG00000143469)

Transcript & Mutation Effects

hg38 • Region Span ~270.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autosomal recessive spinocerebellar ataxia 11LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0013645

Submitter: Labcorp Genetics (formerly Invitae)

autosomal recessive spinocerebellar ataxia 11LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0013645

Submitter: PanelApp Australia

autosomal recessive spinocerebellar ataxia 11SUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0013645

Submitter: Orphanet

Clinical Genomic Database (CGD)

Spinocerebellar ataxia, autosomal recessive 11AR

Manifestation: Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 21835308

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SYT14 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 74

not providedTotal: 53

SYT14-related disorderTotal: 6

Autosomal recessive spinocerebellar ataxia 11Total: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001146262.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	14 clinvar	2 clinvar	19
missense	1 clinvar		74 clinvar	5 clinvar		80
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)		1 clinvar	1 clinvar			2
Total	1	1	78	19	2	101

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 34 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001146262.4	RefSeq	NP_001139734.1	9	MANE Select
ENST00000367019.6	Ensembl	ENSP00000355986.1	9	MANE Select
NM_001146261.4	RefSeq	NP_001139733.1	10	Standard
NM_001146264.4	RefSeq	NP_001139736.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Cellular Component

integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000422431
Coding exons: 10
Length: 226099
Individuals with no LoFs: 125716
Homozygous LoFs: 0
Heterozygous LoFs: 9
Defined: 125725
p: 0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.33	249	316	0.789	0.0000152	4037
Missense (PolyPhen)		42	77.205	0.54401		984
Synonymous	1.23	100	117	0.855	0.00000590	1170
Loss of Function	4.08	4	26.8	0.149	0.00000121	379

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.000026	0.000026	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues. Is Ca(2+)-independent.;

Recessive Scores

pRec: 0.111

Intolerance Scores

LoFtool: 0.294
RVIS EVS: -0.49
RVIS percentile EVS: 22.36

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.659

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium