SERAC1

serine active site containing 1, the group of Armadillo like helical domain containing

Basic information

Region (hg38): 6:158109518-158168280

Links

ENSG00000122335 ∙ NCBI:84947 ∙ OMIM:614725 ∙ HGNC:21061 ∙ Uniprot:Q96JX3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome (Strong), mode of inheritance: AR
• 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome (Supportive), mode of inheritance: AR
• 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome (Definitive), mode of inheritance: AR
• 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome (Strong), mode of inheritance: AR
• Leigh syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome	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	Audiologic/Otolaryngologic; Biochemical; Neurologic	16527507; 22683713; 23707711

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SERAC1 gene.

• 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome (237 variants)
• not provided (152 variants)
• not specified (36 variants)
• Inborn genetic diseases (24 variants)
• SERAC1-Related Disorders (1 variants)
• Mitochondrial oxidative phosphorylation disorder (1 variants)
• Seizure (1 variants)
• SERAC1-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SERAC1 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			5	39	2	46
missense	1	3	91	8	4	107
nonsense	11	4				15
start loss						0
frameshift	8	4	2			14
inframe indel			1			1
splice donor/acceptor (+/-2bp)		1	1			2
splice region		3	12	10		25
non coding	3	1	6	93	44	147
Total	23	13	106	140	50

Highest pathogenic variant AF is 0.000151

Variants in SERAC1

This is a list of pathogenic ClinVar variants found in the SERAC1 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-158111064-ACT-A			Likely benign (Jul 09, 2018)
6-158111108-C-T		3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome	Benign (May 02, 2023)
6-158111155-A-G			Benign (Jun 14, 2018)
6-158111350-T-C		not specified	Benign (Jun 16, 2014)
6-158111364-TGTTA-T		3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome	Uncertain significance (Nov 24, 2022)
6-158111366-T-C		3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome	Uncertain significance (Aug 19, 2022)
6-158111369-G-C		3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome	Uncertain significance (Aug 17, 2021)
6-158111397-C-T		3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome	Uncertain significance (Nov 22, 2022)
6-158111398-G-A		3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome • SERAC1-related disorder	Benign/Likely benign (Dec 09, 2023)
6-158111400-ATGAAT-A		3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome	Uncertain significance (Jul 13, 2022)
6-158111415-C-G		3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome	Conflicting classifications of pathogenicity (Nov 01, 2022)
6-158111415-C-T		3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome	Uncertain significance (Aug 10, 2022)
6-158111416-G-A		3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome	Uncertain significance (Nov 22, 2022)
6-158111455-T-C		Inborn genetic diseases	Uncertain significance (Dec 19, 2022)
6-158111480-A-AT		3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome	Pathogenic (-)
6-158111483-T-C		3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome	Likely benign (Feb 03, 2023)
6-158111485-G-T		3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome	Uncertain significance (May 10, 2023)
6-158111488-C-T			Uncertain significance (-)
6-158111492-A-T		3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome	Uncertain significance (Jun 09, 2022)
6-158111508-G-C		3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome	Uncertain significance (Nov 29, 2022)
6-158113420-C-T			Likely benign (Oct 01, 2022)
6-158113439-G-C		not specified • 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome	Likely benign (Oct 23, 2023)
6-158113439-GAGTGAATACCTGCTGA-CCTGTTGGT		3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome • SERAC1-related disorder	Likely pathogenic (Oct 07, 2022)
6-158113446-T-C		3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome	Uncertain significance (Feb 08, 2018)
6-158113452-C-T		3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome	Uncertain significance (Apr 16, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SERAC1	protein_coding	protein_coding	ENST00000367104	16	58777

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000393	1.00	125637	0	111	125748	0.000441

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.49	278	357	0.778	0.0000187	4271
Missense in Polyphen		66	114.02	0.57885		1308
Synonymous	1.49	100	121	0.828	0.00000630	1240
Loss of Function	3.39	16	38.8	0.412	0.00000225	447

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000907	0.000898
Ashkenazi Jewish	0.00	0.00
East Asian	0.000381	0.000381
Finnish	0.00171	0.00171
European (Non-Finnish)	0.000256	0.000255
Middle Eastern	0.000381	0.000381
South Asian	0.000425	0.000425
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays an important role in the phosphatidylglycerol remodeling that is essential for both mitochondrial function and intracellular cholesterol trafficking. May catalyze the remodeling of phosphatidylglycerol and be involved in the transacylation- acylation reaction to produce phosphatidylglycerol-36:1. May be involved in bis(monoacylglycerol)phosphate biosynthetic pathway. {ECO:0000269|PubMed:22683713}.

Recessive Scores

• pRec: 0.0972

Intolerance Scores

• loftool: 0.440
• rvis_EVS: 0.24
• rvis_percentile_EVS: 69.51

Haploinsufficiency Scores

• pHI: 0.198
• hipred: N
• hipred_score: 0.492
• ghis: 0.468

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.168

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Serac1

Gene ontology

• Biological process: phospholipid biosynthetic process;extracellular matrix organization;intracellular cholesterol transport;phosphatidylglycerol acyl-chain remodeling
• Cellular component: mitochondrion;endoplasmic reticulum;integral component of membrane;extracellular matrix;mitochondria-associated endoplasmic reticulum membrane
• Molecular function: molecular_function