C12ORF57

Chr 12AR

chromosome 12 open reading frame 57

Also known as: C10, GRCC10

This protein is required for corpus callosum development in the brain and is ubiquitously expressed across human tissues. Mutations cause Temtamy syndrome, which is inherited in an autosomal recessive pattern. The gene shows low constraint against loss-of-function variants (pLI ~0, LOEUF 1.86), consistent with its recessive inheritance pattern.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Temtamy syndromeMIM #218340
AR
0
Active trials
1
Pubs (1 yr)
119
P/LP submissions
5%
P/LP missense
1.86
LOEUF
Mechanism
Clinical SummaryC12ORF57
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
74 unique Pathogenic / Likely Pathogenic· 126 VUS of 355 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.86LOEUF
pLI 0.000
Z-score -0.33
OE 1.16 (0.621.86)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.90Z-score
OE missense 1.28 (1.091.51)
102 obs / 79.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.16 (0.621.86)
00.351.4
Missense OE1.28 (1.091.51)
00.61.4
Synonymous OE1.55
01.21.6
LoF obs/exp: 6 / 5.2Missense obs/exp: 102 / 79.5Syn Z: -2.56

ClinVar Variant Classifications

355 submitted variants in ClinVar

Classification Summary

Pathogenic58
Likely Pathogenic16
VUS126
Likely Benign126
Benign15
Conflicting8
58
Pathogenic
16
Likely Pathogenic
126
VUS
126
Likely Benign
15
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
2
48
0
58
Likely Pathogenic
5
2
9
0
16
VUS
5
85
35
1
126
Likely Benign
0
0
66
60
126
Benign
0
0
14
1
15
Conflicting
8
Total188917262349

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

C12ORF57 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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