LCE3C

Chr 1

late cornified envelope 3C

Also known as: LEP15, SPRL3A

NCBI Gene: 353144 ENSG00000244057 UniProt: Q5T5A8 OMIM: 612615

Involved in defense response to Gram-negative bacterium; defense response to Gram-positive bacterium; and killing of cells of another organism. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

Involved in defense response to Gram-negative bacterium; defense response to Gram-positive bacterium; and killing of cells of another organism. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.47

Clinical Summary— LCE3C

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.00) despite low pLI — interpret in context.

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ClinVar Variants

9 VUS of 12 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.47LOEUF

pLI 0.475

Z-score 1.21

OE 0.00 (0.00–1.47)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.94Z-score

OE missense 0.63 (0.48–0.85)

33 obs / 52.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–1.47)

0≤0.351.4

Missense OE?0.63 (0.48–0.85)

0≤0.61.4

Synonymous OE?0.53

0≤1.21.6

LoF obs/exp: 0 / 1.7Missense obs/exp: 33 / 52.1Syn Z: 1.70

This gene — mechanism propensity

0.78top 25%

GOF

0.5464th %ile

LOF

0.2678th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

12 submitted variants in ClinVar

ClinVar

Classification Summary

VUS9

Benign3

VUS

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	9	9
Likely Benign	0	0
Benign	3	3
Total	12	12

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

View in ClinVar →

11 pathogenic / likely-pathogenic (of 17) ClinVar copy-number / structural variants overlap LCE3C — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →