C12orf57

protein-coding

chromosome 12 open reading frame 57

Gene summary

This gene is ubiquitously expressed in human tissues. It is required for development of the human corpus callosum. Mutations in this gene are associated with Temtamy syndrome (TEMTYS). Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2014]

MANE transcript

NM_138425.4

Inheritance

ClinVar variants

P:22U:94B:68

Top phenotype

Temtamy syndrome

gnomAD constraint

pLI —, LoF o/e 1.16

Max pathogenic AF

—

Genomic locus

chr12:6,942,978-6,946,003

External References & Databases

Ensembl (ENSG00000111678)

Transcript & Mutation Effects

hg38 • Region Span ~3.0 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

temtamy syndromeDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009033

Submitter: Ambry Genetics

temtamy syndromeMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0009033

Submitter: Ambry Genetics

temtamy syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009033

Submitter: Labcorp Genetics (formerly Invitae)

temtamy syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009033

Submitter: G2P

Clinical Genomic Database (CGD)

Temtamy syndromeAR

Manifestation: Craniofacial; Neurologic; Ophthalmologic

Intervention: General

Rationale: 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

Refs: 17632789; 21937992; 23453665; 23453666; 23633300; 24798461

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to C12orf57 variants in ClinVar

14 Conditions Cataloged

Temtamy syndromeTotal: 211

not providedTotal: 34

not specifiedTotal: 17

Inborn genetic diseasesTotal: 10

C12orf57-related disorderTotal: 8

Global developmental delayTotal: 2

Intellectual disabilityTotal: 2

Renal atrophyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_138425.4. 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	67 clinvar		68
missense	1 clinvar		89 clinvar	1 clinvar		91
nonsense	3 clinvar	2 clinvar	1 clinvar			6
start loss	1 clinvar	2 clinvar				3
frameshift	6 clinvar	2 clinvar	1 clinvar			9
splice donor/acceptor (+/-2bp)	2 clinvar	3 clinvar	2 clinvar			7
Total	13	9	94	68	0	184

Highest pathogenic variant AF is 0.000029738081

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_138425.4	RefSeq	NP_612434.1	3	MANE Select
ENST00000229281.6	Ensembl	ENSP00000229281.5	3	MANE Select
NM_001301834.1	RefSeq	NP_001288763.1	3	Standard
NM_001301836.2	RefSeq	NP_001288765.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

post-embryonic development
regulation of skeletal muscle contraction
corpus callosum morphogenesis
third ventricle development
psychomotor behavior

Molecular Function

molecular_function

Cellular Component

cytoplasm
nuclear speck

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000229281
Coding exons: 3
Length: 3026
Individuals with no LoFs: 125734
Homozygous LoFs: 0
Heterozygous LoFs: 13
Defined: 125747
p: 0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.897	102	79.5	1.28	0.00000419	811
Missense (PolyPhen)		28	26.549	1.0547		273
Synonymous	-2.56	55	35.6	1.55	0.00000210	261
Loss of Function	-0.331	6	5.19	1.16	2.22e-7	58

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00014	0.00014	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0.000066	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: In brain, may be required for corpus callusum development. {ECO:0000269|PubMed:23453666}.;

Recessive Scores

pRec: 0.109

Intolerance Scores

LoFtool: 0.584
RVIS EVS: -0.12
RVIS percentile EVS: 44.89

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N

Gene Damage Prediction

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