GTF3C3

protein-coding

general transcription factor IIIC subunit 3, the group of General transcription factor IIIC complex subunits|Tetratricopeptide repeat domain containing

Gene summary

The protein encoded by this gene is part of the TFIIIC2 complex, which binds to the promoters of small nuclear and cytoplasmic RNA genes in order to recruit RNA polymerase III. The TFIIIC2 complex is composed of six subunits. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

MANE transcript

NM_012086.5

Inheritance

ClinVar variants

P:10U:88B:10

Top phenotype

neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.4

Max pathogenic AF

—

Genomic locus

chr2:196,763,035-196,799,725

External References & Databases

Ensembl (ENSG00000119041)

Transcript & Mutation Effects

hg38 • Region Span ~36.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

genetic developmental and epileptic encephalopathyLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0100062

Submitter: Ambry Genetics

neurodevelopmental disorderSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

complex neurodevelopmental disorderMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0100038

Submitter: G2P

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GTF3C3 variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 72

Neurodevelopmental disorder with dysmorphic facies, brain anomalies, and seizuresTotal: 12

not providedTotal: 9

GTF3C3-related disorderTotal: 7

Chromosome 2q32-q33 deletion syndromeTotal: 2

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

Neurodevelopmental disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012086.5. 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			1 clinvar	6 clinvar	1 clinvar	8
missense	7 clinvar	1 clinvar	79 clinvar	3 clinvar		90
nonsense	1 clinvar	1 clinvar	1 clinvar			3
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	8	2	88	9	1	108

Highest pathogenic variant AF is 0.000039711744

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 48 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012086.5	RefSeq	NP_036218.1	18	MANE Select
ENST00000263956.8	Ensembl	ENSP00000263956.3	18	MANE Select
NM_001206774.2	RefSeq	NP_001193703.1	9	Standard
ENST00000409364.3	Ensembl	ENSP00000386465.3	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Gene expression (Transcription)
rna polymerase iii transcription
RNA Polymerase III Abortive And Retractive Initiation
RNA Polymerase III Transcription Initiation From Type 1 Promoter
RNA Polymerase III Transcription Initiation From Type 2 Promoter

Biological Process

transcription by RNA polymerase III
5S class rRNA transcription by RNA polymerase III
tRNA transcription by RNA polymerase III
RNA polymerase III preinitiation complex assembly

Molecular Function

RNA polymerase III general transcription initiation factor activity
RNA polymerase III transcription regulator recruiting activity
DNA binding
protein binding

Cellular Component

transcription factor TFIIIC complex
nucleus
nucleoplasm
nucleolus
nuclear membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000263956
Coding exons: 18
Length: 36694
Individuals with no LoFs: 125683
Homozygous LoFs: 0
Heterozygous LoFs: 65
Defined: 125748
p: 0.000258

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.57	321	480	0.669	0.0000249	5826
Missense (PolyPhen)		72	132.23	0.5445		1520
Synonymous	1.89	136	167	0.814	0.00000822	1647
Loss of Function	3.82	19	47.4	0.401	0.00000266	593

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00049	0.00049	rare
Latino/Admixed American	0.00020	0.00020	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00022	0.00022	rare
Finnish	0.00028	0.00028	rare
European (Non-Finnish)	0.00029	0.00028	rare
South Asian	0.00017	0.00016	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in RNA polymerase III-mediated transcription. Integral, tightly associated component of the DNA-binding TFIIIC2 subcomplex that directly binds tRNA and virus-associated RNA promoters.;

Recessive Scores

pRec: 0.246

Intolerance Scores

LoFtool: 0.819
RVIS EVS: -0.42
RVIS percentile EVS: 25.64

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.984

Gene Damage Prediction

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