SYNC

protein-coding

syncoilin, intermediate filament protein, the group of Intermediate filaments Type III

Gene summary

This gene encodes a member of the intermediate filament family which contains an N-terminal head domain, followed by a central coiled-coil region and a short C-terminal tail. The protein is highly expressed in skeletal and cardiac muscle. The protein links the dystrophin associated protein complex (DAPC) to desmin filaments in muscle and may have a structural role in striated muscle. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2009]

Previous symbols:

SYNC1

MANE transcript

NM_030786.3

Inheritance

—

ClinVar variants

U:83B:9

Top phenotype

SYNC-related disorder

gnomAD constraint

pLI —, LoF o/e 0.52

Max pathogenic AF

—

Genomic locus

chr1:32,679,906-32,703,596

External References & Databases

Ensembl (ENSG00000162520)

Transcript & Mutation Effects

hg38 • Region Span ~23.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SYNC variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 82

not providedTotal: 3

SYNC-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_030786.3. 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				2 clinvar		2
missense			81 clinvar	7 clinvar		88
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	83	9	0	92

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 28 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_030786.3	RefSeq	NP_110413.3	5	MANE Select
ENST00000409190.8	Ensembl	ENSP00000386439.3	5	MANE Select
NM_001161708.2	RefSeq	NP_001155180.2	4	Standard
ENST00000373484.4	Ensembl	ENSP00000362583.3	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

intermediate filament-based process

Molecular Function

structural molecule activity

Cellular Component

cytosol
intermediate filament
Z disc
neuromuscular junction
sarcolemma

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000409190
Coding exons: 5
Length: 23691
Individuals with no LoFs: 125718
Homozygous LoFs: 0
Heterozygous LoFs: 30
Defined: 125748
p: 0.000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.668	216	245	0.880	0.0000132	3114
Missense (PolyPhen)		78	92.458	0.84363		1235
Synonymous	1.23	83	98.5	0.843	0.00000504	942
Loss of Function	2.02	11	21.0	0.524	0.00000109	246

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.00018	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00028	0.00027	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Atypical type III intermediate filament (IF) protein that may play a supportive role in the efficient coupling of mechanical stress between the myofibril and fiber exterior. May facilitate lateral force transmission during skeletal muscle contraction. Does not form homofilaments nor heterofilaments with other IF proteins. {ECO:0000250|UniProtKB:Q9EPM5}.;

Intolerance Scores

LoFtool: 0.205
RVIS EVS: 1.48
RVIS percentile EVS: 95.31

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0573

Gene Damage Prediction

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