ETV3L

Chr 1

ETS variant transcription factor 3 like

NCBI Gene: 440695 ENSG00000253831 UniProt: Q6ZN32 OMIM: 621105

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific. Predicted to be involved in cell differentiation and regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.42

Clinical Summary— ETV3L

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Population Constraint (gnomAD)

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

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ClinVar Variants

63 VUS of 86 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.42LOEUF

pLI 0.000

Z-score 0.43

OE 0.88 (0.56–1.42)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.35Z-score

OE missense 1.07 (0.96–1.20)

217 obs / 203.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.88 (0.56–1.42)

0≤0.351.4

Missense OE?1.07 (0.96–1.20)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 12 / 13.7Missense obs/exp: 217 / 203.1Syn Z: -0.14

This gene — mechanism propensity

0.75top 25%

GOF

0.5366th %ile

LOF

0.4529th %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

86 submitted variants in ClinVar

ClinVar

Classification Summary

VUS63

Likely Benign15

Benign4

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	0	63	0	63
Likely Benign	1	12	2	15
Benign	0	2	2	4
Total	1	77	4	82

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

View in ClinVar →

11 pathogenic / likely-pathogenic (of 13) ClinVar copy-number / structural variants overlap ETV3L — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →