RNASEH2C

ribonuclease H2 subunit C

Basic information

Region (hg38): 11:65714004-65720818

Links

ENSG00000172922 ∙ NCBI:84153 ∙ OMIM:610330 ∙ HGNC:24116 ∙ Uniprot:Q8TDP1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Aicardi-Goutieres syndrome 3 (Definitive), mode of inheritance: AR
• Aicardi-Goutieres syndrome 3 (Strong), mode of inheritance: AR
• Aicardi-Goutieres syndrome 3 (Strong), mode of inheritance: AR
• Aicardi-Goutieres syndrome (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Aicardi-Goutieres syndrome 3	AR	General	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	Cardiovascular; Gastrointestinal; Dermatologic; Hematologic; Neurologic	16845400; 17846997; 20301648; 23322642

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RNASEH2C gene.

• Aicardi-Goutieres syndrome 3 (277 variants)
• not provided (28 variants)
• Inborn genetic diseases (11 variants)
• Aicardi Goutieres syndrome (5 variants)
• not specified (4 variants)
• RNASEH2C-related condition (2 variants)
• Abnormality of the nervous system (1 variants)
• Neurodevelopmental disorder (1 variants)
• Neurodevelopmental disorder with dysmorphic facies, sleep disturbance, and brain abnormalities (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RNASEH2C 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			1	57	2	60
missense		3	106	1		110
nonsense		2				2
start loss						0
frameshift			8			8
inframe indel			2	1		3
splice donor/acceptor (+/-2bp)			1			1
splice region			5	6		11
non coding			46	42	7	95
Total	0	5	164	101	9

Highest pathogenic variant AF is 0.00000657

Variants in RNASEH2C

This is a list of pathogenic ClinVar variants found in the RNASEH2C region.

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

Position	Type	Phenotype	Significance	ClinVar
11-65714512-T-C			Likely benign (Oct 01, 2022)
11-65714532-C-T		not specified	Uncertain significance (Jan 19, 2024)
11-65714726-T-A		Neurodevelopmental disorder with dysmorphic facies, sleep disturbance, and brain abnormalities	Uncertain significance (Aug 25, 2022)
11-65714734-G-C		not specified • Neurodevelopmental disorder with dysmorphic facies, sleep disturbance, and brain abnormalities	Uncertain significance (Aug 18, 2023)
11-65716922-T-A		Neurodevelopmental disorder with dysmorphic facies, sleep disturbance, and brain abnormalities	Pathogenic (Dec 04, 2020)
11-65716981-CAGTG-C		Neurodevelopmental disorder with dysmorphic facies, sleep disturbance, and brain abnormalities	Uncertain significance (Jun 29, 2021)
11-65717686-G-A		Aicardi-Goutieres syndrome 3	Benign (Jan 13, 2018)
11-65717747-G-A		Aicardi-Goutieres syndrome 3	Benign (Jan 12, 2018)
11-65717806-G-A		Aicardi-Goutieres syndrome 3	Uncertain significance (Jan 13, 2018)
11-65717866-A-G		Aicardi-Goutieres syndrome 3	Benign (Jan 12, 2018)
11-65717952-C-T		Aicardi-Goutieres syndrome 3	Uncertain significance (Jan 13, 2018)
11-65717977-C-T		Aicardi-Goutieres syndrome 3	Uncertain significance (Jan 12, 2018)
11-65718005-G-C		Aicardi-Goutieres syndrome 3	Uncertain significance (Jan 13, 2018)
11-65718007-G-A		Aicardi-Goutieres syndrome 3	Benign (Jan 13, 2018)
11-65718015-G-A		Aicardi-Goutieres syndrome 3	Uncertain significance (Jan 13, 2018)
11-65718046-G-A		Aicardi-Goutieres syndrome 3	Uncertain significance (Jan 13, 2018)
11-65718084-C-G		Aicardi-Goutieres syndrome 3	Uncertain significance (Jan 13, 2018)
11-65718125-C-G		Aicardi-Goutieres syndrome 3	Uncertain significance (Jan 13, 2018)
11-65718162-T-C		Aicardi-Goutieres syndrome 3	Benign (Jan 13, 2018)
11-65718189-C-T		Aicardi-Goutieres syndrome 3	Uncertain significance (Jan 13, 2018)
11-65718251-C-T		Aicardi-Goutieres syndrome 3	Uncertain significance (Jan 12, 2018)
11-65718256-T-G		Aicardi-Goutieres syndrome 3	Benign (Jan 13, 2018)
11-65718279-C-T		Aicardi-Goutieres syndrome 3	Uncertain significance (Jan 12, 2018)
11-65718405-C-G		Aicardi-Goutieres syndrome 3	Uncertain significance (Jan 13, 2018)
11-65718488-A-G		Aicardi-Goutieres syndrome 3	Benign/Likely benign (May 14, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RNASEH2C	protein_coding	protein_coding	ENST00000308418	4	6052

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00550	0.732	125737	0	11	125748	0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.917	122	96.6	1.26	0.00000463	1037
Missense in Polyphen		38	34.385	1.1051		370
Synonymous	-1.41	54	42.3	1.28	0.00000219	356
Loss of Function	0.791	4	6.11	0.655	2.73e-7	69

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000153	0.000153
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000598	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000634	0.0000615
Middle Eastern	0.0000598	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Non catalytic subunit of RNase H2, an endonuclease that specifically degrades the RNA of RNA:DNA hybrids. Participates in DNA replication, possibly by mediating the removal of lagging- strand Okazaki fragment RNA primers during DNA replication. Mediates the excision of single ribonucleotides from DNA:RNA duplexes. {ECO:0000269|PubMed:16845400, ECO:0000269|PubMed:21177858}.
• Pathway: DNA replication - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.114

Intolerance Scores

• loftool: 0.277
• rvis_EVS: -0.05
• rvis_percentile_EVS: 49.39

Haploinsufficiency Scores

• pHI: 0.0824
• hipred: N
• hipred_score: 0.296
• ghis: 0.577

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.910

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rnaseh2c
• Phenotype: growth/size/body region phenotype; embryo phenotype; skeleton phenotype; vision/eye 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); pigmentation phenotype

Gene ontology

• Biological process: RNA catabolic process
• Cellular component: nucleus;ribonuclease H2 complex