SMG6

SMG6 nonsense mediated mRNA decay factor, the group of Endoribonucleases

Basic information

Region (hg38): 17:2059838-2303785

Previous symbols: [ "C17orf31" ]

Links

ENSG00000070366 ∙ NCBI:23293 ∙ OMIM:610963 ∙ HGNC:17809 ∙ Uniprot:Q86US8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SMG6 gene.

• Inborn genetic diseases (63 variants)
• not provided (8 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SMG6 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				3	1	4
missense			58	5	4	67
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	58	8	5

Variants in SMG6

This is a list of pathogenic ClinVar variants found in the SMG6 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-2061511-G-A		not specified	Uncertain significance (Jan 08, 2024)
17-2061521-C-G		not specified	Uncertain significance (Oct 27, 2023)
17-2061532-C-T		not specified	Uncertain significance (Oct 22, 2021)
17-2065075-T-C		not specified	Uncertain significance (Mar 01, 2023)
17-2065082-C-T		not specified	Likely benign (Aug 04, 2023)
17-2065475-C-T		not specified	Uncertain significance (Feb 05, 2024)
17-2065500-C-T		not specified	Uncertain significance (Feb 22, 2023)
17-2065554-G-A		not specified	Uncertain significance (Jun 02, 2023)
17-2065592-C-T		not specified	Uncertain significance (Feb 27, 2024)
17-2065632-G-A		not specified	Uncertain significance (Aug 02, 2021)
17-2065642-C-G		not specified	Uncertain significance (Feb 05, 2024)
17-2065662-C-T		not specified	Uncertain significance (Sep 20, 2023)
17-2065673-T-C		not specified	Uncertain significance (Jul 20, 2022)
17-2068825-G-A		not specified	Uncertain significance (Jun 29, 2023)
17-2068889-C-T			Benign (May 29, 2018)
17-2068927-A-G		not specified	Uncertain significance (Oct 02, 2023)
17-2081834-C-A		not specified	Uncertain significance (Sep 23, 2023)
17-2081881-C-G		not specified	Uncertain significance (Jun 07, 2023)
17-2081910-T-C		not specified	Uncertain significance (Oct 20, 2021)
17-2081926-C-T			Benign (May 08, 2018)
17-2085771-A-G		not specified	Uncertain significance (Nov 09, 2023)
17-2172663-C-T		not specified	Uncertain significance (May 08, 2023)
17-2172746-A-G		not specified	Uncertain significance (Jan 09, 2024)
17-2172770-G-A		not specified	Uncertain significance (Jun 22, 2021)
17-2172790-C-G		not specified	Uncertain significance (Jul 11, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SMG6	protein_coding	protein_coding	ENST00000263073	19	243933

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.982	0.0184	125717	0	31	125748	0.000123

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.178	820	834	0.983	0.0000530	9251
Missense in Polyphen		269	331.94	0.81039		3583
Synonymous	-2.27	373	321	1.16	0.0000191	2809
Loss of Function	6.10	12	65.1	0.184	0.00000376	745

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000148	0.000148
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000163	0.000109
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000168	0.000167
Middle Eastern	0.000163	0.000109
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the telomerase ribonucleoprotein (RNP) complex that is essential for the replication of chromosome termini (PubMed:19179534). May have a general role in telomere regulation (PubMed:12676087, PubMed:12699629). Promotes in vitro the ability of TERT to elongate telomeres (PubMed:12676087, PubMed:12699629). Overexpression induces telomere uncapping, chromosomal end-to-end fusions (telomeric DNA persists at the fusion points) and did not perturb TRF2 telomeric localization (PubMed:12676087, PubMed:12699629). Binds to the single-stranded 5'-(GTGTGG)(4)GTGT-3' telomeric DNA, but not to a telomerase RNA template component (TER) (PubMed:12676087, PubMed:12699629). {ECO:0000269|PubMed:12676087, ECO:0000269|PubMed:12699629, ECO:0000269|PubMed:19179534}.
• Pathway: mRNA surveillance pathway - Homo sapiens (human);Regulation of Telomerase (Consensus)

Recessive Scores

• pRec: 0.149

Intolerance Scores

• loftool: 0.240
• rvis_EVS: -0.16
• rvis_percentile_EVS: 42.06

Haploinsufficiency Scores

• pHI: 0.493
• hipred: Y
• hipred_score: 0.792
• ghis: 0.528

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.497

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Smg6
• Phenotype: embryo phenotype; growth/size/body region phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cellular phenotype

Zebrafish Information Network

• Gene name: smg6
• Affected structure: extension
• Phenotype tag: abnormal
• Phenotype quality: decreased thickness

Gene ontology

• Biological process: nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;mRNA export from nucleus;telomere maintenance via telomerase;regulation of telomere maintenance;regulation of telomere maintenance via telomerase;regulation of dephosphorylation;regulation of RNA stability;regulation of telomerase activity;RNA phosphodiester bond hydrolysis, endonucleolytic;negative regulation of telomere capping
• Cellular component: chromosome, telomeric region;nucleus;telomerase holoenzyme complex;nucleolus;cytoplasm;cytosol;exon-exon junction complex
• Molecular function: RNA binding;endoribonuclease activity;protein binding;telomeric DNA binding;ribonucleoprotein complex binding;metal ion binding;telomerase RNA binding;DNA polymerase binding