C12ORF57

Chr 12

chromosome 12 open reading frame 57

Also known as: C10, GRCC10

NCBI Gene: 113246 ENSG00000111678 UniProt: Q99622

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.

ResearchSummary from RefSeq, OMIM, UniProt

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]

ResearchGenerating clinical summary…

LOEUF 1.86

Clinical Summary— C12ORF57

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

28 unique Pathogenic / Likely Pathogenic· 120 VUS of 306 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.86LOEUF

pLI 0.000

Z-score -0.33

OE 1.16 (0.62–1.86)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.90Z-score

OE missense 1.28 (1.09–1.51)

102 obs / 79.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.16 (0.62–1.86)

0≤0.351.4

Missense OE?1.28 (1.09–1.51)

0≤0.61.4

Synonymous OE?1.55

0≤1.21.6

LoF obs/exp: 6 / 5.2Missense obs/exp: 102 / 79.5Syn Z: -2.56

ClinVar Variant Classifications

306 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14

Likely Pathogenic14

VUS120

Likely Benign127

Benign18

Conflicting8

Pathogenic

Likely Pathogenic

120

VUS

127

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	11	2	1	0	14
Likely Pathogenic	7	2	5	0	14
VUS	5	88	26	1	120
Likely Benign	0	0	67	60	127
Benign	0	0	17	1	18
Conflicting	—				8
Total	23	92	116	62	301

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

View in ClinVar →

47 pathogenic / likely-pathogenic (of 59) ClinVar copy-number / structural variants overlap C12ORF57 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →